Je n'arrive pas a envoyé un PM mais je voulais savoir si je pouvais avoir le password svp?
I can not sent a PM but I wanted to know if I could have the password please?
Last edited by tkk7406 on 17 Sep 2016 14:48, edited 1 time in total.
Wenn möglich würde ich mich auch über das Passwort freuen.
If possible I would also welcome the password.
Last edited by tkk7406 on 17 Sep 2016 14:47, edited 1 time in total.
It's written for users, not for author. Start reading descriptions and readme files and you won't have problems.
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00:02:30.077 : Cargo 'Frango Congelado' does not have any trailer data and will be ignored.
00:02:30.077 : Cargo 'Equipamentos Mergulho' does not have any trailer data and will be ignored.
00:02:30.077 : Cargo 'Eletrodomesticos' does not have any trailer data and will be ignored.
00:02:30.077 : Cargo 'Etanol_' does not have any trailer data and will be ignored.
00:02:30.077 : Cargo 'Diesel' does not have any trailer data and will be ignored.
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00:02:52.314 : <ERROR> [traffic_area] Traffic area with uid 0x66F114C77D00001 has no valid attributes set!
00:02:52.594 : Map successfully loaded.
00:02:53.582 : Road network navigation caching started.


This report describes a technique and the outcome following surgical revision of a periprosthetic infected total hip replacement (THR) in a single-stage procedure with the use of antibiotic-impregnated bioabsorbable beads. A 6-year-old German Shepherd dog underwent THR 16 months previously, which subsequently became infected. The contaminated femoral and acetabular prostheses were explanted. A femoral window was used to remove the stem and cement. The endosteal surfaces of the femur and acetabulum were reamed to remove periprosthetic tissues. The femoral window was replaced and secured in position with multiple cerclage wires. A 3.5-mm locking plate was applied to the lateral aspect of the femur to prevent fracture of the proximal femoral metaphysis and trochanter. Bioabsorbable beads of calcium sulphate, impregnated with vancomycin and gentamicin, were impacted into the femoral canal followed by an uncemented femoral stem. An uncemented acetabular implant was impacted and additional antibiotic beads placed in the vicinity prior to closure. There has been no evidence of reinfection 5 years postoperatively. Analgesic and antibacterial drugs were not required during this follow-up period; activity is unrestricted with neither lameness nor pain present. Simultaneous revision of both femoral and acetabular periprosthetic infected THR implants was successfully achieved in this patient via a single-stage procedure using uncemented implants and antibiotic-impregnated bioabsorbable beads.


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VfB Theley is a German association football club from the Theley suburb of the town of Tholey, Saarland. The club's greatest success has been promotion to the second tier 2. Oberliga Südwest in 1958 where it played for five seasons. After the introduction of the Bundesliga in 1963 Theley spent another three seasons at the second tier, now the Regionalliga Südwest before dropping out of higher level football altogether in 1974.

Theley also made two appearances in the DFB-Pokal, in 1974–75 and 1976–77, but was knocked out in the second round at each occasion.

History
Football was established in Theley after the First World War when British soldiers were stationed in the village for a number of weeks to demarcate the boundary between Germany and the soon to be League of Nations-administrated Saarland and were spotted playing the game by local youth. The club played as a local amateur side for the first couple of decades of its existence.

VfB Theley won promotion to the tier three Amateurliga Saarland in 1955 and spent the first two seasons as a lower table side before winning the league in 1957–58. Promoted, Theley played in the 2. Oberliga Südwest the next five season from 1958 to 1963, playing as a lower table side with two eleventh-place finishes as its best result.

Back in the Amateurliga Theley won the league in 1970 and 1972, earning promotion to the tier two Regionalliga on each occasion. The club spent three seasons in the Regionalliga Südwest, in 1970–71 and from 1972 to 1974 with a tenth place in 1973 as its best result. At the end of the 1973–74 season the Regionalliga was disbanded in favour of the new 2. Bundesliga and the club dropped out of higher league football altogether.

In the period that followed Theley made two appearances in the first round of the DFB-Pokal, in 1974–75 and 1976–77. In Both instances the club advanced to the second round where it was knocked out by Altonaer FC 93 and MSV Duisburg. In its first two Amateurliga seasons Theley finished runners-up in the league and fourth in 1977 but, in 1977–78, when a top-seven finish was required to qualify for the new Oberliga the club came only thirteenth. Because of this it dropped to the new tier four Verbandsliga Saarland, but was relegated from this level the following season as well.

Theley returned to the Verbandsliga in 1981 but was relegated in 1984. It returned for a second time in 1988, generally achieving better results that culminated in a league championship in 1998–99. Promoted, the club played for a single season in the Oberliga Südwest in 1999–2000 but finished eighteenth and was relegated again. Back in the Verbandsliga Theley played as a lower table side until 2007 when it was relegated to the Landesliga. When the Saarlandliga was introduced as the new highest league in the state, as the sixth tier of the league system, the club moved back up to the expanded Verbandsliga. From there it won promotion to the Saarlandliga where it spent the 2010–11 season. Relegated back to the Verbandsliga Theley experienced another drop in 2015, now to the Landesliga. A runners-up finish in the Landesliga in 2015–16 took the club back up to the Verbandsliga.

Honours
The club's honours:
 Amateurliga Saarland
 Champions: 1957–58, 1969–70, 1971–72
 Verbandsliga Saarland
 Champions: 1998–99, 2009–10
 Saarland Cup
 Winners: 1975–76

Recent seasons
The recent season-by-season performance of the club:

 With the introduction of the Regionalligas in 1994 and the 3. Liga in 2008 as the new third tier, below the 2. Bundesliga, all leagues below dropped one tier.

References

External links
Official club site
VfB Theley at Weltfussball.de

Football clubs in Germany
Football clubs in Saarland
Association football clubs established in 1919
1919 establishments in Germany

redpajama_set_name: RedPajamaWikipedia


Flu season is here and it's likely that you or a family member will contract some kind of illness before the season ends. But it's still worth the effort to avoid getting sick! And that begins with knowing what's true about the flu.
Myth 1 – You can catch a cold from being outside in cold weather.
Many people still believe that going out in the cold without a coat will make you sick.
More people do get sick during the colder months, but being out in cold weather only makes you feel colder.
Staying indoors can actually increase your chances of catching a cold because you're in closer proximity with others who could be contagious.
Myth 2 – You can get a cold only from someone who sneezes or coughs close to you.
When an infected person sneezes or coughs near you, their illness can spread from one person to another. But that's not the only way germs spread.
Direct contact with someone who has a cold is even more likely to make you sick.
Hand-to-hand contact is the most common way to spread viruses several studies show.
Myth 3 – Your cold can turn into the flu.
Different viruses cause the flu and the common cold. A cold can't "morph" into the flu.
Both have similar symptoms, so it can be hard to tell the difference between them.
The flu is much worse than a cold. Symptoms like fever, body aches and extreme fatigue are more intense.
Myth 4 – The flu isn't that serious.
Serious complications and death result every year from the flu.
Children under 5, adults over 65, pregnant women and those with chronic illnesses are at higher risk for complications.
Myth 5 – A flu shot can give you the flu.
No, a flu shot cannot cause flu illness. Vaccines are made from viruses that have been "inactivated" and are therefore not infectious.
Myth 6 – If you don't get a flu shot by January, it's too late.
It's never too late to get a flu shot during flu season, which usually peaks in February, but can run through May. The shot protects you, and those around you who are at more risk.
Myth 7 – There's no way to reduce the length of a cold or flu.
The key to cutting the flu short is to act right away. If you can see your doctor within the first 48 hours of infection, you may be able to cut down the number of sick days.
QualChoice members can get the flu vaccine at any network pharmacy or provider's office with no copayment**.


(Crain's) — Retired Commonwealth Edison CEO Frank Clark, former Chicago buildings Commissioner Mary Richardson-Lowry and investor Bruce Rauner are among the candidates for the Cook County hospital board, which was created four years ago to end decades of patronage and mismanagement.
Cook County Board President Toni Preckwinkle is unlikely to reappoint two current members of the board of the Cook County Health and Hospitals System who have expressed an interest in staying on, according to people familiar with the selection process.
Board Chairman Warren Batts, a retired executive, and Dr. David Ansell, chief medical officer at Rush University Medical Center, are expected to leave the board when their four-year terms expire on June 30.
Ms. Preckwinkle has two additional vacancies to fill on the 11-member board. Ruth Rothstein, a former CEO of Mount Sinai Hospital who in December filled a board vacancy with a term expiring on June 30, also is stepping down. Sister Sheila Lyne, CEO of Mercy Hospital and Medical Center, whose term doesn't expire until next year, wants to resign, the spokeswoman for Ms. Preckwinkle said.
Ms. Rothstein, who also was chief of what was then known as the Cook County Bureau of Health Services, said she was not interested in another term. A spokeswoman for Sister Lyne did not respond to a message seeking comment.
The new wave of appointments comes as the independent board reaches a crossroads. It was created in 2008 during the tumultuous administration of former Cook County Board President Todd Stroger, part of a controversial compromise with county board Commissioner Larry Suffredin that paved the way for a 1 cent increase in the county sales tax.
Since her election in 2010, Ms. Preckwinkle led the effort to repeal the sales tax hike and has sought to bring better management throughout county government.
The appointments give the budget-minded Ms. Preckwinkle an opportunity to shape a board that largely was formed to insulate county health care from the County Board president's office, protecting the health system from political influence while improving management, which had been in disarray.
While the hospital board is charged with overseeing the direction of the sprawling health care system, with operating revenue of $488 million in 2011, Ms. Preckwinkle controls the purse strings.
• Ms. Richardson-Lowry, now a partner at law firm Mayer Brown LLP, former Chicago buildings commissioner and past president of the Chicago Board of Education.
• Mr. Clark, who in March was named by Mayor Rahm Emanuel to the board of the Metropolitan Pier and Exposition Authority, one month after retiring from ComEd.
• Mr. Rauner, a principal at private-equity firm GTCR LLC and chairman of the Chicago Convention & Tourism Bureau.
• Carmen Velasquez, executive director of Alivio Medical Center, a network of Southwest Side clinics.
• Anthony Barbato, a retired CEO of Loyola University Medical Center who is now affiliated with Oak Brook-based executive search firm Witt/Kieffer.
• Dorene Wiese, president of American Indian Association of Illinois.
• Karen Batia, executive director of Heartland Health Outreach, a nonprofit that serves low-income patients.
• Berneice Mills-Thomas, executive director, Near North Health Service Corp., a network of community clinics.
• Edward Michael, executive vice president of diagnostics at North Chicago-based Abbott Laboratories.
• Rev. Calvin Morris, executive director of the Community Renewal Society, a Chicago nonprofit organization.
The Cook County hospital system is one of the largest public hospital systems in the nation and treats a largely uninsured and Medicaid population. Heavily dependent on government funding, the system struggles to generate revenue and depends on county taxpayers for a subsidy — $252 million for 2012 — to help stay afloat.
The network, which includes Stroger and Provident hospitals, had a $148 million deficit during the fiscal year that ended Nov. 30, according to the Civic Federation, a fiscal watchdog group.
Mr. Batts and Dr. Ansell said hiring CEO Ramanathan Raju last year, creating a strategic plan and making unpopular but cost-saving decisions, such as layoffs and the conversion of Oak Forest Hospital into an outpatient facility, were among the board's top accomplishments.
Besides continuing to steer a financially-strapped system, the new board members will have to find ways to attract and retain patients who become insured in 2014 through the Affordable Care Act and can shop for care, and ensure the system can provide services, as some patients now wait months for routine procedures.
Ms. Velasquez, who founded Alivio nearly 24 years ago, said her background in running a grassroots organization that provides care for the poor and underinsured makes her a good fit for a board that oversees a safety-net hospital system with a similar mission.
Ms. Richardson-Lowry said a busy schedule might prevent her from serving on the board. Mr. Clark declined to comment. The remaining candidates did not return calls seeking comment.
The spokeswoman for Ms. Preckwinkle said the county board president plans to submit four nominees to the County Board during a June 19 meeting and hopes commissioners approve the nominees the same day.


Born in 1973,Bursa,Uğur Çelikkol has acquired a taste for sightseeing and photography which he inherited from his father and made it part of his life.By constantly exploring new destinations,he has improved himself to a great extent with regard to sightseeing and culture tours.
Rafet Çelikkol,a skier and one of the first voluntary tourism professionals in Bursa,set up Karagöz Antique in 1960-a souvenir shop- where Uğur Çelikkol learnt the basics of tourism and its culture. Currently, he is working with his father at Karagöz Antika in Eski Aynalı Çarşı, dealing in antiques such as handcrafts,Karagöz figurines,embroideries,and other artefacts. After having gratuated from Foreign Languages Department,Uludag University,he attended a certificate programme in organizing tours and in tourism english by Bosphorus University. He has been a registered tour guide by Ministery of Culture and Tourism since 1992 and with the advantage of being in the tourism for years, he has been able to create an archive of photography intended for both professionals and amateurs with different aims.Some of the photos taken by Çelikkol are those covering cultural aspects of our traditional shadow play,Karagöz, Bursa and its environs,Istanbul,both sides of the Aegean Sea.He has been a member of Bufsad-Bursa Photography Society since 1998.
He is also one of the family members who have done their best to revive the traditional shadow play, Karagöz art,in which he is an expert.He is a member of Unima Turkey (International Puppetry and Shadow Play Union) and he is the general secratary of Unima Bursa,which is the second branch in Turkey.He is the only person from Unima Bursa who paid a visit to Unima headquarters located in Charleville Mezieres,France. He himself and his familiy have contributed a lot to Bursa Karagöz Theatre by attending the festivals both at home and abroad,thus having had the opportunity to promote our traditional shadow puppet theatre, Karagöz.His father,Şinasi Çelikkol,has made great efforts to draw the public's attention to Karagöz House founded by R.Şinasi ÇELİKKOL just across from the Karagöz Monumental Grave on the Çekirge Street.
Çelikkol who combines his photography passion with his profession and social surroundings is one of the senior members of the Bufsad. Celikkol worked as a newsreader at Olay TV between 01 February 2005 and 30 June 2007.
He attended many group exhibitions , held his own exhibitions, gave many photos to travel journals and documentarily books and brochures and he also gave conferences accompanied by slights at various festivals at home and abroad . You can find most of his articles published in various magazines and newspapers about the culture in Bursa on the internet . Celikkol wrote articles accompanied by the photographs he took for the Daily Bursa Hakimiyet on its Sunday editions between November 2008 and May 2011 .Then he gave a break and started again in October 2012 and he is still contributing to Bursa Hakimiyet. In addition, Celikkol started writing articles on sports for Hurriyet Bursa Edition in 2012 and at the end of 2012 he was transferred to Milliyet newspaper where he is still contributing articles about sports and Bursaspor.
He is organizing tours through Karagöz Travel which he himself established for both domestic tourists and tourists from abroad to destinaitons like Bursa and its surrroundings , and the places from Greece to Syria. Internet address: www.karagoztravel.com Çelikkol has pursued the developments in the tourism of Bursa and carried out the task of general secretariat of Türsab (South Marmara Regional Executive Board) successfully between January 2008 and July 2008.
One of the founder members of Gümred (South Marmara Professional Tourist Guides Association) which came into being in August,2008, Ugur Çelikkol became the first president of the union and tried to do his best to bring all the guides together.He managed to set up an internet web page not witnessed at any other associations.
Uğur Çelikkol was elected as one of the delegates to the Board at the general meeting of IRO held in September,2012,Istanbul.
A team consisting of Tureb,Iro,Aro,Izro presidents together with other unions' representatives led by Şerif Yenen,the president of IRO and Tureb,met with the minister of Culture and Tourism, the politicians and the other people responsible many times,carried out some studies and made painstaking efforts to make the related act to be passed at the parliament.As a result, "Guiding Profession Act" ,which was was passed at a special session in the parliament in June,12012 ,was welcomed by all the guides across Turkey.Uğur Çelikkol was one of those who contributed to the Guiding Profession Act to be carried out.
Çelikkol is specialized in the following areas: walking tours in Bursa and İstanbul, the islands of İstanbul (Kınalı, Burgaz, Heybeli, Buyukada) the islands of Marmara (Marmara, Paşalimanı, Avşa, Ekinlik) the islands of Aegean (Bozcaada, Gökceada, Midilli-Lesvos, Sakız-Chios, Samos-Sisam, Kos, Rodos-Rhodes) ceramics in İznik and Kütahya; Early Ottoman Architecture buildings in Bursa-Edirne-İstanbul and environs, Turkmen yoruk villages around Bursa, handcrafts,organized art tours and workshops, Thracian and Aegean region and the cultures belonging to them,and he is also an expert at tours to mainland Greece and the islands. In addition, he has improved himself a lot regarding Orthodox culture and living styles of Bursa , İstanbul and Marmara region by his own efforts and by attending seminars given by IRO and he is an expert at Turkish Greek population exchanges.
Ugur Celikkol started introducing the inhabitants of Bursa to village tours in 1998-1999 by giving the message " We should know the city we live in by touring the town and its surroundings " and in time, he expanded the scope of daily tours by including one night accomodation tours nearby Bursa within reach. He has brought many dwellers in Bursa to meet the natural beauties and the unfamiliar cultures of our country.


Who wants to carry around a bunch of extra weight when the sweat generated from triple-digit temperatures is already slowing you down? A summer salad topped with fruit or light vinaigrette is the perfect way to satisfy your appetite while staying nimble in the August heat.
Local peach salad at Mary Eddy's Kitchen, Friday, July 28, 2017.
Located in 21c Museum Hotel, Mary Eddy's earned its reputation for combining local ingredients with a modern flair. Its local peach salad is the perfect starter on the dinner menu after a long, hot day. The salad combines bitter mustard greens with aged and salty speck ham and local peaches. No fruit signifies the arrival of summer like a sweet peach. The starter is then topped with blue cheese from Barren County, Kentucky; hazelnuts for crunch; and honey-lemon vinaigrette.
Kale and quinoa salad at Pepperoni Grill, Thursday, July 27, 2017.
Pepperoni Grill is a gem inside Penn Square Mall. Its kale and quinoa salad is an entrée-sized way to escape the heat. It is made with red seedless grapes, mandarin oranges and golden raisins for a refreshing burst of sweetness. Add in red bell peppers, roasted almonds and Parmesan cheese, and its main ingredients have the savory partners for a healthy meal chock full of antioxidants. The salad is topped with champagne vinaigrette for a pleasant, acidic kick.
Locally owned with six locations and a seventh opening soon at Will Rogers World Airport, Cool Greens has found success providing convenient, high-quality meals. The menu features an array of sandwiches, flatbreads and quinoa bowls, but perhaps its signature dishes are its salads, which can also be ordered as wraps. The Plaza Skinny combines mixed greens and peppery arugula with avocado, sundried tomatoes, sunflower seeds and salty artichokes and is topped with basil vinaigrette.
Patrono Salad at Patrono, Thursday, July 27, 2017.
Patrono Italian Restaurant is more than just one of the best Italian eateries in Oklahoma City. Located in the mixed-use center connected to Avana Arts District apartments, the atmosphere is classy yet relaxed. Its namesake salad features mixed greens, fennel, thinly sliced radishes and haricots verts (a fancy name for green beans) and is topped with red and golden beets, ricotta salata and a spicy mustard dressing.
Fresh strawberry and spinach salad at Cafe 501, Wednesday, July 26, 2017.
Strawberry and spinach salad comes two ways at Cafe 501, but the entrée topped with chicken earns our recommendation for a filling and refreshing summer treat. It combines healthy ingredients with a little fried treat in the form of crispy goat cheese. It also includes hearts of palm, carrots and sugared walnuts. The greens are dressed with balsamic vinaigrette and olive oil. With locations in Classen Curve on NW Grand and in Edmond, there is ample opportunity to try this refreshing salad.
Mediterranean curried chicken salad at Paseo Grill, Thursday, July 27, 2017.
One of the qualifiers to make this list was to find a vehicle for summer fruit, and the Mediterranean curried chicken salad at Paseo Grill finds multiple ways to get it on your plate. The chicken salad bursting with curry deliciousness is topped with mango chutney and is joined by a healthy portion of strawberries and red grapes. Fresh pita bread allows you to turn that salad into a sandwich.
Kale and sweet potato salad at Chef Curry To Go, Thursday, July 27, 2017.
Executive chef Kendall Curry is so confident in his food that his name goes on his business, and for good reason. The sweet potato and kale salad takes two ingredients more associated with winter and elevates them to summer status with a sweet caramelized onions and a lemon hoisin reduction. You can add garbanzo beans, chicken or shrimp to make this salad an entrée-sized portion.


The stock has retraced 0% from its recent high price of 45.18 which occurred on 21-Dec-2012. A close below 20-day moving average of 44.82 could mark todays high of 45.18 as recent high.
The stock has recovered 6.1% from its recent low price of 5.26 which occurred on 15-Nov-2012. The current price is above the 50 day moving average of 5.46. Sustained move above the average could signal development of an uptrend.
The stock has recovered 13.7% from its recent low price of 18.31 which occurred on 16-Nov-2012. The current price is above the 50 day moving average of 20.54. Sustained move above the average could signal development of an uptrend.
The stock has recovered 7.8% from its recent low price of 0.102 which occurred on 26-Nov-2010. A close above 20-day moving average of 0.24 could mark low of 0.102 as a recent low.
The stock has recovered 27.9% from its recent low price of 4.81 which occurred on 9-Nov-2012. A close above 20-day moving average of 6.85 could mark low of 4.81 as a recent low.
The stock has retraced 7.5% from its recent high price of 26.24 which occurred on 9-Oct-2012. The current price is below the 20 day moving average of 24.56. The stock could possibly find support at the 50 day moving average of 23.64.


Every living organism depends on enzymes for survival.
In nature, wild animals are continually replenishing digestive enzymes through the ingestion of freshly-killed prey. When enzymes are not present in the right amount your pet may be unable to properly digest his food which could effectively rob him of valuable nutrients. Eventually, your pet may become enzyme-deficient and vulnerable to disease. The lack of digestive enzymes may eventually cause nutritional, digestive, and immune-related problems that can lead to severe disease states. Not surprisingly, glands and major organs suffer most from enzyme deficiency.
Of the three major classes of enzymes, digestive enzymes are responsible for breaking down food into its constituent nutrients for the body to utilize. Different enzymes break down different foods. When enzyme stores are low, it is harder for the digestive system to break down fats, protein, and carbohydrates. Poor digestion can cause pets to suffer from constipation, diarrhea, flatulence and more. Wholistic Digest-All Plus™ is a unique enzyme blend of pure, freeze-dried, plant and plant-based enzymes with added maximum concentrations of prebiotics and probiotics. Formulated for maximum digestive support!
By replenishing your pet's digestive enzyme supply at every feeding, your pet may avoid potential long-term health problems while unlocking available nutrients in both feed and other added supplements.
Mix in your pets regular meal. Daily amount may be divided amongst meals. Amount can be adjusted according to individual dogs needs.


text:
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Revelations grow on Joe Biden's handling of classified documents; here's what we know so far
Francesca Chambers Josh Meyer
Correction & clarification: A previous version of this story misstated the home state of Sen. Chris Coons. He is from Delaware.
WASHINGTON – The revelation that the FBI found additional classified documents during a Friday search of the president's personal residence in Delaware is stoking new scrutiny of Joe Biden's handling of sensitive and in some cases classified information.
Attorneys for Biden stressed in statements on Saturday evening that the president is cooperating with the Department of Justice and special counsel investigation and said the search of his Wilmington, Delaware, residence was voluntary.
The FBI called it planned and consensual in a statement.
But the search, which the president's legal team waited to disclose until a full day later, is generating new questions about White House transparency on the issue that Biden last week suggested is insignificant.
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What do we know about Joe Biden's classified documents?
More than a dozen classified documents have been discovered in Biden's personal offices.
An initial batch of documents was discovered at the Biden Penn Center last year, just prior to the midterm elections. Their existence was not made public by the White House. CBS reported on the documents in January, prompting a congressional inquiry.
A subsequent search of Biden's beach home turned up no additional documents, the White House said.
However, attorneys for Biden found six pages of classified material at his Wilmington residence. And at least six more documents were uncovered during a secondary search of Biden's home that was conducted Friday by the DOJ. Biden attorney Bob Bauer says some handwritten notes from his vice presidential years were also taken into possession.
"Every day it seems like they're finding more documents." Rep. Michael McCaul, R-Texas, on CNN's "State of the Union." "Although it was consensual, the search ... the FBI conducted the search, not his attorneys. That really ratchets the investigation up."
"I think he should have a lot of regrets," said Sen. Joe Manchin, D-W.Va., on NBC's Meet the Press.
"There is one important document that distinguishes former President Trump from President Biden, that's a warrant," said Sen. Chris Coons, D-Del.., on ABC's "This Week," pointing out that the search in Biden's home was voluntary.
"When Joe Biden says he has no regrets, I mean, this is very concerning here," said Rep. James Comer, R-Ky., chairman of the House Oversight Committee on Fox News' "Sunday Morning Futures." "We need to know who had access to those documents."
"Why did he have these? Who did he show them to?" said Rep. Mike Turner, R-Ohio., on CBS' "Face the Nation."
What happened at Biden's Delaware home?
Late Saturday, the Justice Department confirmed that the FBI spent most of the day and night Friday conducting a "planned, consensual search" of Biden's Wilmington home.
Biden was not there for the search, which the White House says took place from early morning until 10:30 at night. He is spending the weekend at his Rehoboth Beach property in Delaware.
An official said the search was not the subject of any court-authorized process, including an approved search warrant at Biden's home.
The latest search:More Biden documents found after DOJ searches his Delaware home
How is this different from Trump's handling of classified documents?
A judge in Florida approved a warrant in early August in a similar investigation into the personal possession of classified documents involving former President Donald Trump. Judges only authorize such search warrants if the requesting authorities show reason to believe that either a crime had been committed there or that evidence of such a crime could be found there.
The Mar-a-Lago warrant authorized FBI agents – accompanied by a Justice Department prosecutor – to search Mar-a-Lago, Trump's Palm Beach, Florida, home and private club, and cart off dozens of boxes of documents. There was no warrant in the search of Biden's residence last week.
The Mar-a-Lago search was conducted only after months of back and forth between Trump and the National Archives and Justice Department, which wanted him to return classified documents that he had indicated he had in his possession. Trump refused, saying he had personally declassified some if not all of them under his broad authorities as president, and that they were part of his personal papers.
Did the FBI raid Biden's home?
No, the search was consensual, expected and coordinated between both parties. The Mar-a-Lago search also was not a raid, though it was conducted on the basis of a court-approved warrant.
Biden administration officials have sought to portray themselves as being much more proactive and cooperative than lawyers for Trump, voluntarily searching his residences and offices in recent weeks in an effort to turn up more potentially problematic documents. They have been accused, however, of not being transparent enough about the searches and what classified documents Biden had in his possession.
Under the Presidential Records Act of 1978, all documents created by the president, vice president and their large staff, including the National Security Council, are the property of the American public and are supposed to be secured by the National Archives. After the National Archives processes the massive volume of documents, many of them are eventually declassified and made available to the public, including at presidential libraries.
A bigger issue?:Biden and Trump documents expose wider problem: Missing classified records not uncommon
What does this mean for Joe Biden?
Democrats have been frustrated by the drip, drip, drip nature of the disclosures.
Although they do not see the situation, which is markedly different than the DOJ's criminal investigation into Trump, as detrimental to Biden's long-term reelection prospects, Democrats such as former House Intelligence Chairman Adam Schiff have supported the appointment of a special counsel to oversee the case.
Biden had been enjoying a bounce in his approval rating and was enjoying increased support from independent voters and nonvoters as the document drama was brewing. New developments in the document scandal could cut into Biden's support as he prepares to give his State of the Union address in early February and potentially announce a reelection bid.
Despite the president's assertions that "there's nothing there" and the "American people don't quite understand" the continued focus on his documents, a Quinnipiac University poll found that 60% of Americans think he handled them inappropriately and two-thirds of Americans are following media coverage.
More:Biden documents probe means US has 3 special counsel investigations at once. What are they?
Poll: What's going to happen in Washington over the next 2 years? Americans don't expect much.
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redpajama_set_name: RedPajamaCommonCrawl


The Indian Institute of Management Bangalore (IIMB) is a leading graduate school of management in Asia. Under the IIM Act of 2017, IIMB is an Institute of National Importance. IIMB has around 100 full time faculty members, more than 1200 students across various long duration programs and nearly 5000 annual Executive Education participants.


text:
Information on EC 2.7.12.2 - mitogen-activated protein kinase kinase
for references in articles please use BRENDA:EC2.7.12.2
2 Transferases
2.7 Transferring phosphorus-containing groups
2.7.12 Dual-specificity kinases (those acting on Ser/Thr and Tyr residues)
2.7.12.2 mitogen-activated protein kinase kinase
This enzyme is a dual-specific protein kinase and requires mitogen-activated protein kinase kinase kinase (MAPKKK) for activation. It is required for activation of EC 2.7.11.24, mitogen-activated protein kinase. Phosphorylation of MEK1 by Raf involves phosphorylation of two serine residues . Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
All organisms Actinidia arguta Adeno-associated virus Aedes Aedes aegypti Aeromonas Aggregatibacter actinomycetemcomitans Agrobacterium tumefaciens Alchornea cordifolia Allium sativum Aloe vera Alternaria brassicicola Alternaria tenuissima amphibia Angiostrongylus cantonensis animal Anopheles stephensi Anthrax Apis mellifera Arabidopsis Arabidopsis thaliana Arabidopsis thaliana Col-0 Ardisia Areas Areca Argynnis pandora Arthrodermataceae Arthropoda Artocarpus altilis Aspergillus flavus Aspergillus nidulans Astronotus ocellatus Aureobasidium pullulans Avian avulavirus 1 Avian carcinoma virus Azadirachta indica Azumapecten farreri Bacilli Bacillus Bacillus anthracis Bacteria Bambuseae Bassia scoparia bat Beauveria bassiana Beta vulgaris Betanodavirus sp. BEV proteobacterium Bifidobacterium breve Bifidobacterium longum Bipolaris maydis Bivalvia Borago officinalis Borrelia Bos taurus Botrytis cinerea Botrytis cinerea 38B1 Bouea macrophylla Bovine orthopneumovirus Brachypodium Brachypodium distachyon Brassica napus Brassica oleracea var. capitata Brassica oleracea var. italica Brassica rapa Brassicaceae Buddleja cordata Byrsonima crassifolia Caenorhabditis elegans Calluna vulgaris Camellia sinensis Candida albicans Candida dubliniensis Canine parvovirus Canis lupus familiaris Capra hircus Capsicum annuum Carassius auratus Castanea sativa Cavia Cavia porcellus Cell fusing agent virus Cervidae Cetacea Chlamydia Chlamydia trachomatis Chlamydiae Chondrichthyes Ciona Ciona intestinalis Citrullus lanatus subsp. vulgaris Citrus Citrus limon Citrus reticulata Classical swine fever virus clinical samples Clostridium perfringens Coffea Coffea arabica Colletotrichum gloeosporioides Compacta Corynebacterium glutamicum Corynebacterium pseudotuberculosis Corynebacterium xerosis Cotyledon Coxsackievirus B3 Cricetinae Cricetulus griseus Croton Cryphonectria hypovirus 1 Cryphonectria parasitica Ctenopharyngodon idella Cucumber necrosis virus Cucumis sativus Cucurbitaceae Cupiennius salei Curcuma longa Cyclopia intermedia Cyprinus carpio Danio rerio Daphne genkwa Daphnia pulex Dengue virus Dictyostelium Dictyostelium discoideum Didelphidae Diptera Drosophila Drosophila melanogaster Ebola virus Echinococcus Echinococcus multilocularis Ecklonia cava Ecotropic murine leukemia virus Elaphoglossum biolleyi Empetrum nigrum var. japonicum enterovirus Enterovirus A71 Epichloe festucae Epicoccum Epinephelus coioides Equus caballus Escherichia coli eukaryota Exserohilum turcicum Favites chinensis Felis catus Filifactor alocis Firmicutes Formicidae Fungi Fusarium graminearum Fusarium oxysporum Galleria mellonella Gallus gallus Garcinia mangostana Ginkgo biloba Glossina morsitans Glycine max Glycyrrhiza Gossypium hirsutum Gryllotalpa gryllotalpa Guinea Helicobacter pylori Hepacivirus C Hepatitis B virus Hericium erinaceus Hippocampus Hippophae rhamnoides Homo sapiens Hordeum vulgare Human alphaherpesvirus 1 Human alphaherpesvirus 2 Human alphaherpesvirus 3 Human gammaherpesvirus 4 Human gammaherpesvirus 8 Human immunodeficiency virus 1 Human rhinovirus sp. Hydra Indicator Intracisternal A-particles Ipomoea batatas Jatropha curcas Jembrana disease virus Juniperus communis Kaempferia parviflora Lactobacillus Lactobacillus helveticus Lactobacillus plantarum Lactobacillus reuteri Lamina Leishmania Leishmania amazonensis Leishmania chagasi Leishmania major Leishmania mexicana Leishmania tropica Lentivirus Lethrinidae Listeria monocytogenes Lolium perenne Lonicera caerulea Lonicera japonica Lotus japonicus Loxosceles Loxosceles arizonica Macaca fascicularis Macaca mulatta Macaca mulatta polyomavirus 1 Macaca mulatta rhadinovirus Machilus thunbergii Magnoliophyta Maize streak virus Malpighia glabra Malus domestica Mammalia Manduca Manduca sexta Mangifera indica marmosets Marmota monax Martes zibellina Medicago Medicago sativa Melasma Melicope grisea Meloidogyne artiellia Mesocricetus auratus Mesorhizobium loti Metarhizium rileyi Metazoa Micrococcus luteus Mizuhopecten yessoensis Moringa oleifera Morus alba Mus musculus Mus sp. Musa acuminata Musculus Mustela lutreola Mycobacterium Mycobacterium lepraemurium Mycobacterium tuberculosis Mycobacterium tuberculosis variant bovis BCG Mycobacterium ulcerans Myrsinaceae Nardostachys jatamansi Nematoda Nematodes Neurospora Neurospora crassa Nicotiana Nicotiana attenuata Nicotiana benthamiana Nicotiana rustica Nicotiana tabacum Notolabrus celidotus Ogataea minuta Ophiopogon japonicus Opuntia humifusa Orcinus orca Oryctolagus cuniculus Oryza sativa Oryza sativa Indica Group Oryza sativa Japonica Group Oryzias latipes Ovis aries Panax ginseng Papio anubis Paronychia Patinopecten sp. Pectinidae Penaeus chinensis Penaeus vannamei Penicillium commune Perilla frutescens Peromyscus Peromyscus maniculatus Persea americana Physcomitrella patens Phytomonas oxycareni Phytophthora Phytophthora parasitica Pieris brassicae Pimenta pseudocaryophyllus Pinus pinaster Piper retrofractum plant Plasmodiophora brassicae Plasmodium falciparum Platyhelminthes Platyrrhini Poaceae Podospora anserina Polypodium Populus Populus trichocarpa Porcine sapovirus Porifera Porphyromonas Porphyromonas endodontalis Porphyromonas gingivalis Primates prion Prunus persica Pseudomonas Pseudomonas aeruginosa Pseudomonas cichorii Pseudomonas syringae Puma concolor Punica granatum Purpura Pyrenophora graminea Ralstonia solanacearum Raphanus sativus Rattus Rattus norvegicus Reovirus sp. Respiratory syncytial virus Rhodobacter sphaeroides Rice stripe tenuivirus Rodentia Rosa multiflora Ross River virus Rous sarcoma virus Rubiaceae Saccharomyces Saccharomyces cerevisiae Saccharomycetales Saccharomycetes Salicornia brachiata Salmo salar salmon Salmonella enterica Salmonella enterica subsp. enterica serovar Typhimurium Salvia miltiorrhiza Sapovirus Sargassum muticum Schisandra chinensis Schizosaccharomyces Schizosaccharomyces pombe Scleroderma Sclerotia Scutellaria baicalensis Septa Serinus canaria Shigella shrimp Shrimp white spot syndrome virus Silybum marianum Simian immunodeficiency virus Singapore grouper iridovirus snake Solanaceae Solanum lycopersicum Solanum tuberosum Sordaria macrospora Sphinx Spondias purpurea Sporothrix schenckii Staphylococcus aureus Staphylococcus carnosus Staphylococcus epidermidis Streptococcus pneumoniae Stylissa massa Suidae Sus scrofa Synapsis Syzygium aromaticum Taiwanofungus camphoratus Tephritidae Tetrapoda Theobroma cacao Thrombus Tinea tobacco mosaic virus Tobacco rattle virus Toona sinensis Toxoplasma gondii Trichoderma atroviride Trichoderma cremeoides Trichoderma viridarium Trichophyton mentagrophytes Triticeae Triticum aestivum Trypanosoma brucei Trypanosoma brucei brucei Trypanosoma brucei brucei 927/4 Trypanosoma cruzi Ursidae Ustilago maydis Vaccinia virus vertebrata Verticillium Verticillium dahliae Verticillium dahliae XS11 Vibrio anguillarum Vibrio parahaemolyticus Vigna radiata var. radiata Vigna unguiculata subsp. cylindrica Viruses Vitis amurensis Vitis vinifera Vulpes vulpes white spot syndrome virus Xanthomonas oryzae Xanthomonas oryzae pv. oryzicola Xenopus Xenopus laevis yeasts Yellow fever virus Yersinia Zea mays Zea mays subsp. mays Zingiber officinale Zizania latifolia Ziziphus jujuba
3-kinase
phosphatidylinositol
phorbol
dominant-negative
rapamycin
uvb-induced
stress-activated
keratinocytes
wortmannin
phosphoinositide
caspase-3
corneum
platelet-derived
demethylase
cyclooxygenase-2
percutaneous
erythema
neurotrophic
erk-dependent
mek-erk
dual-specificity
uvb-irradiated
p38mapk
signal-related
photoprotective
extracellular-regulated
p90rsk
egf-induced
photodamage
kinase-independent
ras-dependent
p38alpha
brafv600e
p21ras
ras-mediated
phospho-erk
The enzyme appears in viruses and cellular organisms
a protein
a phosphoprotein
mek/erk, map kinase kinase, mapkk, mek-1, extracellular-signal-regulated kinase, mapk/erk kinase, erk 1, map2k4, mitogen-activated protein kinase kinase 1, erk 2, more
apoptosis signal-regulating kinase 1
O35099
ASK1
Q8RXG3
BcOs4
P0CY25
cdc7 protein kinase
Cdc7p kinase
cell division control protein 7
cpkk1
Cryphonectria parasitica
; gene name
B2ZAW3
DMKK4
dual specificity mitogen-activated protein kinase kinase 1
dual specificity mitogen-activated protein kinase kinase dSOR1
dual specificity mitogen-activated protein kinase kinase hemipterous
dual specificity mitogen-activated protein kinase kinase mek-2
dual specificity protein kinase FUZ7
ERK 1
Mesocricetus auratus
extracellular signal-regulated kinase
extracellular-signal-regulated kinase
extracellular-signal-regulated kinase 1
GhMKK3
Gossypium hirsutum
S4S5K3
HEP protein
JNKK1
mammalian MAP kinase kinase
Cricetulus griseus
MAP kinase kinase
MAP kinase kinase 4
MAP kinase kinase homologue
Leishmania mexicana
Q9GRT1
MAP kinase kinase MKK1/SSP32
MAP kinase kinase skh1/pek1
Q9Y884
B2ZAW3, O93876
MAP2K4
MAP3K11
MAPK kinase
MAPK kinase 1
MAPK kinase kinase-1
MAPK kinase-1
MAPK/Erk kinase
MAPK/ERK kinase 1
MAPKK
MAPKK 1
Q5QN75
MAPKK 10-2
A2XE35
A3FK65
Q0MSI2
Q0Z7Z4
MAPKK1
MAPKKK5
MEK 1
MEK kinase 1
Q9Y2U5
MEK-1
MEK/ERK
MEK1/2
MEK4,
MEKK 2
MEKK-1
MEKK1
mitogen activated kinase kinase
mitogen activated protein kinase kinase
mitogen activated protein kinase kinase 6
mitogen-activated protein kinase kinase
mitogen-activated protein kinase kinase 1
Q8CE90
mitogen-activated protein kinase kinase 7gamma1
mitogen-activated protein kinase kinase homologue
mitogen-activated protein kinase kinase kinase 1
mitogen-activated protein kinase kinase kinase 11
Q9Y6R4
mitogen-activated protein kinase kinase type 2
mitogen-activated protein kinase kinase-1
mitogen-activated protein kinase kinase/extracellular signal–regulated kinase
mitogen-activated protein kinase/ERK kinase kinase 3
mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1
mitogen-activated protein/ERK kinase kinases
MKK homologue
MKK1
MKK4/SEK1
MKK7gamma1
OsMKK1
OsMKK10-2
p120cdc7 protein kinase
p21cdc42/rac1 binding protein
Pfnek3
polymyxin B resistance protein kinase
protein kinase byr1
protein kinase wis1
SAPK/ERK kinase-1
SAPKK3
SEK1
serine/threonine protein kinase STE7
serine/threonine protein kinase STE7 homolog
serine/threonine-protein kinase PAK 2
Q9P286
Sip2
Lotus japonicus
F8THZ4
SMG1
Oryza sativa Japonica Group
Q0DWY3
stress kinase mitogen-activated protein kinase kinase 7
stress-activate protein kinase/extracellular signal-regulated protein kinase kinase-1
Tb927.10.5270
Tb927.3.4860
TUB4
VdPbs2
wis1 protein kinase
XMEK2
ZmMKK1
Q94EV7
Botrytis cinerea
I7FWY1
Botrytis cinerea 38B1
A2XE35, A3FK65, Q0MSI2, Q0Z7Z4, Q5QN75
P47809, Q8CE90
Arabidopsis thaliana Col-0
P52564, Q02750
A2XE35, A3FK65, A5A544, I3RJI6
Verticillium dahliae
Verticillium dahliae XS11
I3L5D4
A2XE35, A3FK65, A5A544, I3RJI6, Q0Z7Z4
Trypanosoma brucei brucei
Q38B76, Q582P9
Trypanosoma brucei brucei 927/4
A9UK00
Q94A06
Q582P9
Q9S7U9
Q38B76
I3RJI6
MKK3 is a group B MAPK kinase
the enzyme belongs to the MKK familly
ATP + a protein = ADP + a phosphoprotein
ATP:protein phosphotransferase (MAPKKK-activated)
This enzyme is a dual-specific protein kinase and requires mitogen-activated protein kinase kinase kinase (MAPKKK) for activation. It is required for activation of EC 2.7.11.24, mitogen-activated protein kinase. Phosphorylation of MEK1 by Raf involves phosphorylation of two serine residues [5]. Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
ATP + a protein
ADP + a phosphoprotein
ATP + BcSak1
ADP + phosphorylated BcSak1
ATP + c-Jun N-terminal kinase
ADP + phosphorylated c-Jun N-terminal kinase
ATP + casein
ADP + phosphorylated casein
ATP + ERK
ADP + phospho-ERK
ADP + phosphorylated ERK
ATP + Erk-1 gene product
ADP + phosphorylated Erk-1 gene product
phosphorylation primarily on a tyrosine residue and, to a lesser extent, on a threonine
ATP + ERK1
ADP + phosphorylated ERK1
ATP + ERK1/2
ADP + phosphorylated ERK1/2
ATP + extracellular regulated kinase 1
ADP + phosphorylated extracellular regulated kinase 1
ATP + GhMPK7
ADP + phosphorylated GhMPK7
ATP + Janus kinase 2
ADP + phospho-Janus kinase 2
ATP + JNK
ADP + JNK phosphate
ADP + phopsho-JNK
the enzyme is involved in stress-activated MAP kinase pathways, tumorigenesis, and cancer acting as a metastasis suppressor, overview
ADP + phospho-JNK
ADP + phosphorylated JNK
ATP + JNK1
ADP + phosphorylated JNK1
ATP + K52R-[ERK2]
ADP + phospho-K52R-[ERK2]
catalytically inactive ERK2 in which lysine-52 is substituted with arginine
ATP + K53M-[p38alpha]
ADP + phospho-K53M-[p38alpha]
catalytically inactive p38alpha in which lysine-53 is substituted with methionine
ATP + KIMPK3
ADP + phosphorylated KIMPK3
ATP + MAP kinase
ADP + phosphorylated MAP kinase
ATP + MAP kinase 6
ADP + phosphorylated Map kinase 6
Arabidopsis thaliana MAP kinase MPK6
ATP + MAP kinase ERK1
ADP + ?
ATP + MAPK
ADP + phosphorylated MAPK
ATP + MKK4
ADP + phosphorylated MKK4
ATP + MPK-7
ADP + phospho-MPK-7
ATP + myelin basic protein
ADP + phoshorylated myelin basic protein
ADP + phosphorylated myelin basic protein
ATP + myelin basic protein kinase
ADP + phosphorylated myelin basic protein kinase
ATP + MyoD
ADP + phospharylated MyoD
ATP + p38
ADP + p38 phosphate
ADP + phospho-p38
ADP + phosphorylated p38
ATP + p38 MAP kinase
phosphorylates and activates p38 MAP kinase
ATP + p38/MPK2 kinase
phosphorylates and specifically activates the p38/MPK2 subgroup of the mitogen-activated protein kinase superfamily
ATP + p38alpha
ADP + phosphorylated p38alpha
MKK6 phosphorylates p38 MAPK on Thr180 and Tyr182, the sites of phosphorylation that activate p38 MAPK
ATP + Pfmap2
ADP + phosphorylated Pfmap2
the enzyme phosphorylates its potential in vivo Pfmap2 substrate largely on Thr290
ATP + poly-(Tyr-Glu)
ADP + phospho-poly-(Tyr-Glu)
tyrosine kinase substrate
ATP + protein
ADP + phosphoprotein
ATP + Red1
ADP + phospho-Red1
substrate of Mek1
ATP + Smad3
ADP + phosphorylated Smad3
ATP + VdHog1
ADP + phosphorylated VdHog1
ATP + [ERK2 substrate peptide]
ADP + [ERK2 substrate peptide] phosphate
ATP + [myelin basic protein substrate peptide]
ADP + [myelin basic protein substrate peptide] phosphate
MKK1 phosphorylates and activates the MAP kinases ERK1 and ERK2
protei BcSAK1 is the putative downstream component of BOS5
JNK activation
ERK phosphorylation by MEK1/2
phosphorylation by MEK activates ERK, which plays a role in pain induction modulating the A-type currents of potassium channels in neurons, ERK plays a central role in nocireceptive sensitization in the spinal cord
ERK phosphorylation by MEK
MEK2 protein stimulates Thr and Tyr phosphorylation on ERK1 and concomitantly activates ERK1 kinase activity more than 100-fold
phosphorylation of extracellular signal-regulated kinase 1
MEK1 is able to effectively phosphorylate Thr183 and Tyr185 in the activation loop of ERK2
O14733, P45985
the enzyme is involved in stress-activated MAP kinase pathways, tumorigenesis, and cancer, physiologic effects, overview
substrate of MKK4 and MKK7 in a synergistic manner
the enzyme is involved in stress-activated MAP kinase pathways and tumorigenesis, overview
phosphorylation of JNK at the Thr residue located in the activation loop
phosphorylation of JNK at the Tyr residue located in the activation loop
slight phosphorylation, JNK1 may not be the optimal substrate for the isoform
activation of MAP kinase
the enzyme is involved in the mitogen-activated protein kinase signaling pathway important for e.g. flagellar length control, the enzyme is involved in differentiation of the parasite and is important for virulence and infection of human peritoneal macrophages
docking site for the substrate is located close to the N-terminal Lys4 and consists of 2 basic amino acid residues separated by a spacer of 2-6 variable residues from an L/I/V-X-L/I/V sequence
MAPK activation
MKK3 interacts with MPK7 in planta
Pfnek3 phosphorylates MBP on threonine, but not serine residues
phosphorylation at Tyr156, activated MEK1 associates with MyoD
phosphorylation at Tyr156 recombinant GST-tagged MyoD substrate. Mutational analysis of phosphorylation sites using MyoD Tyr mutants, overview
substrate of MKK7
substrate of MKK4 and MKK7
activation by phosphorylation
signal cascade upstream activation by phosphorylation, sorbitol induced activation of p38 in salmon TO cells does not require MKK6a, b or c
mek-2 acts between lin-45 raf and sur-1/mpk-1 in a signal transduction pathway used in the control of vulval differentiation and other developmental events
Hst7 activates the mating pathway even in the absence of upstream signaling components including the Ste7 regulator Ste11, elevates the basal level of the pheromone-inducible FUS1 gene, and amplifies the pseudohyphal growth response in diploid cells
the enzyme functions in a novel Drosophila MAPK pathway, controlling puckered expression and morphogenetic activity of the dorsal epidermis
the enzyme is involved in the mitogenic growth factor signal transduction pathway in vertebrates
P45985, P46734
enzyme is involved in independent human MAP-kinase signal transduction pathway
MKK4 may participate in a tumor suppressive signaling pathway distinct from DPC4, p16, p53, and BRCA2. The enzyme is a component of a stress and cytokine-induced signal transduction pathway involving MAPK proteins, additional role for MKK4 in tumor suppression
the enzyme is an activator of the c-Jun NH2-terminal kinase, the enzyme is a component of the JNK signal transduction pathway
enzyme is the major activator for p38
enzyme is involved on MAPK signal transduction pathway
the enzyme is the major activator of RK/p38
MEKK3 regulates the SAPK and the ERK pathway directly
ASK1 may be a key element in the mechanism of stress-induced and cytokine-induced apoptosis
MEK6 is a member of the p38 kinase cascade and efficiently phosphorylates p38, induces phosphorylation of ATF2 by p38 but does not phosphorylate ATF2 directly
MAPKKK5 may be an upstream activator of MKK4 in the c-Jun N-terminal kinase pathway
sequences located in the N-terminus of MEK5 may be important in coupling GTPase signaling molecules to the MEK5 protein kinase cascade
phosphorylates kinase-inactive Erk-1 protein primarily on a tyrosine residue and, to a lesser extent, on a threonine
possible role for ASK1 in tissue development during embryogenesis as well as cytokine-induced apoptosis
Q61083, Q61084
MEKK 2 preferentially activates JNK
MEKK 3 preferentially activates p42/44MAPK
tyrosine/threonine kinase
the enzyme renders the cell resistant to polymyxin B
MKK1 and MKK2 function in a signal transduction pathway involving the protein kinases encoded by PKC1, BCK1, and MPK1. The site of action for MKK1 and MKK2 is between BCK1 and MPK1
enzyme is involved in the response of haploid yeast cells to peptide mating pheromones
Pek1, in its unphosphorylated form, acts as a potent negative regulator of Pmk1 MAPK signalling. Mkh1, an upstream MAPKK kinase, converts Pek1 from being an inhibitor to an activator. Pek1 has a dual stimulatory and inhibitory function which depends on its phosphorylation state
enzyme plays a key role in initiation of septum formation and cytokinesis in fission yeast, p120cdc7 interacts with the cdc11 protein in the control of septation
dosage-dependent regulator of mitosis in Schizosaccharomyces pombe
Spg1p is a key element in controlling the onset of septum formation that acts through the Cdc7p kinase
byr1 is an important gene in the sexual differentiation pathway and at least part of ras1 function is to act directly or indirectly through byr1 to modulate protein phosphorylation
the enzyme is a component of the mkh1 signaling pathway. Mkh1, Skh1 and Spm1 constitute a MAPK cascade in Schizosaccharomyces pombe
the enzyme is required for locus-dependent and locus-independent steps in the fungal life cycle. Necessary for locus-dependent processes, such as conjugation tube formation, filament formation, and maintenance of filamentous growth, and for locus-independent processes, such as tumor induction and teliospore germination
the enzyme undergoes autophosphorylation on Ser, Thr and Tyr
the enzyme functions as a direct upstream activator for a presumed MAP kinase homolog in each signal transduction pathway involved in the regulation of cell cycle progression or cellular responses to extracellular signals
mitogen-activated protein kinase kinase-1 regulates SMAD3 expression in epithelial and smooth muscle cells, which is stimulated by TGFbeta-1, SMAD3 is a transcription factor that mediates TGF-?1 signaling and is important in many of the cellular processes that regulate fibrosis and inflammation, overview
VdHog1 is a mitogen-activated protein kinase, MAPK
Arabidopsis thaliana mitogen-activated protein kinase kinase MKK1 is implicated in biotic and abiotic stress responses as part of a signaling cascade including MEKK1 and MPK4, MKK1 and MKK2 function upstream of MPK4, overview. The mkk1/2 double mutant is similar to the mpk4 mutant, as both: (1) are dark green dwarves with curled leaves, (2) constitutively overproduce salicylic acid and exhibit enhanced resistance to biotrophic pathogens and insensitivity to JA, and (3) have enhanced basal expression of PR1 and other SA-dependent defense genes
Arabidopsis thaliana mitogen-activated protein kinase kinase MKK2 is implicated in biotic and abiotic stress responses as part of a signaling cascade including MEKK1 and MPK4, MKK1 and MKK2 function upstream of MPK4, overview. mkk2 single mutants appear morphologically normal, the mkk1/2 double mutant is similar to the mpk4 mutant, as both: (1) are dark green dwarves with curled leaves, (2) constitutively overproduce salicylic acid and exhibit enhanced resistance to biotrophic pathogens and insensitivity to JA, and (3) have enhanced basal expression of PR1 and other SA-dependent defense genes
MKK3 positively regulates PR gene expression and plays a role in defense against Pst DC3000. MKK3 is an upstream activator of the group C MAPKs MPK1, MPK2, MPK7, and MPK14, overview
substrate binding via the D-domain of the MKK
enzyme is part of mitogen-activated protein kinase pathways, crosstalk and regulation mechanism, overview
GhMKK3 interacts with GhMPK7, a typical C group MAPK member, and GhPIP1 potein. GhMPK7 is phosphorylated by GhMKK3 in protoplasts
MEKK3 activates SEK and MEK, the known kinases targeting SAPK and ERK respectively
MEK1/2 are involved in the mitogen-activated protein kinase signaling pathway and in cancer tumorigenesis
the enzyme is involved in the mitogen-activated protein kinase signaling pathway, which is linked to the cell cycle machinery, constitutive phosphorylation and activation of the enzyme leads to cell proliferation in choroidal melanoma cells
MKK7gamma1 is unable to phosphorylate p38
mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma it is required for growth of fibrosarcoma-derived xenografts, to maintain tumor blood flow, and for vascularization of fibrosarcoma-derived xenografts, and MKK signaling is required for the release of proangiogenic factors from other sarcoma-derived cell lines, overview
pro-oncogenic role of mitogen-activated protein kinase kinase 4 in cancer, overview
the MEKK-1 is involved in stress-induced cell death of insulin-producing cells and essential in JNK activation, overview
TNF-alpha receptor signaling regulates epithelial cell secretion of inflammation and invasion mediators involving signaling through IkappaB kinase complex 2, IKB, nuclear factor kappaB, extracellular signal-regulated kinase, mitogen-activated protein kinase kinase, p38, and phosphatidylinositol 3-kinase, and Akt1/2. MEK, p38, and IKK inhibitors block TNF-alpha-induced IL-8, IL-6, and GM-CSF secretion and 12z invasion, whereas the PI3K inhibitors do not, overview
MKK signaling is required for cell proliferation and for cytokine release in vitro
development of a continuous spectrophotometric assay for mitogen-activated protein kinase kinases. The assay relies on the measurement of phosphoprotein product generated in the first step of the MAPK kinase reaction. Dephosphorylation of the phosphoprotein is coupled to a MAPK phosphatase, MKP3, to generate phosphate, which is then used as the substrate of purine nucleoside phosphorylase to catalyze the N-glycosidic cleavage of 2-amino 6-mercapto 7-methyl purine ribonucleoside. Of the reaction products ribose 1-phosphate and 2-amino 6-mercapto 7-methylpurine, the latter has a high absorbance at 360 nm relative to the nucleoside and, hence, provides a spectrophotometric signal that can be continuously followed. In the presence of excess phosphatase, the phosphorylated protein substrate molecules undergo dephosphorylation almost immediately after their formation. The steady-state use of the resultant inorganic phosphate is a reflection of the constant initial velocity of the exchange reaction. Method development and evaluation, overview
the enzyme performs autophosphorylation
the enzyme is involved in the mitogen-activated protein kinase signaling pathway regulating cell dissociation of cancer cells, MEK2 is an invasion-metastasis related factor between highly and weakly invasive cells, occludin acts as antagonist
the enzyme is involved in the mitogen-activated protein kinase signaling pathway, which is involved in e.g. formalin-induced inflammatory pain and thermal hyperalgesia, overview
pro-oncogenic role of mitogen-activated protein kinase kinase 4 in cancer, overview. MKK4 is also involved in the immune system and development of B- and T-cells, as well as in cardiac hypertrophy, overview
MKK4 phosphorylates JNK on Tyr, while MKK7 phosphorylates Thr, and MKK4 and MKK7 together cause dual phosphorylation of JNK thus, optimal activation
MAP kinase kinase 1 is regulated by salt and drought stresses, differential expression, overview
MAP kinase kinase 10-2 is regulated only by cold stress, differential expression, overview
MAP kinase kinase 6 is strongly regulated by cold and salt stresses, differential expression, overview
MAP kinase kinases 4 is strongly regulated by cold and salt stresses, differential expression, overview
regulation and differential expression, overview
protein-protein docking of MAPKK and MAPK
the enzyme displays both serine/threonine and tyrosine kinase activities in autophosphorylation reactions as well as in phosphorylation of the exogenous myelin basic protein substrate. Ability of Pfnek3 to autophosphorylate on both the serine/threonine and the tyrosine residues. The dual-specificity activity of the kinase is distinctly influenced by the type of divalent cation present
the enzyme is involved in the mitogen-activated protein kinase signaling pathway
the enzyme is involved in the mitogen-activated protein kinase signaling pathway, pathway induction by neurotrophin stabilizes the axonal growth cone, pathway inhibitor semaphorin 3F induces growth cone collaps in sympathetic neurons and reduction of axonal growth
the enzyme is involved in the mitogen-activated protein kinase signaling pathway, which is involved in e.g. activation of Egr-1 and subsequently of c-Fos and cyclin D1 after mechanic injury for induction/regulation of regrowth of smooth vascular cells, vascular smooth muscle cell proliferation plays an important role in pathogenesis of atherosclerosis and post-angioplasty restenosis, overview
adenosine-stimulated adrenal steroidogenesis involves the adenosine A2A and A2B receptors and the Janus kinase 2-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase signaling pathway, overview
lithium protection of phencyclidine-induced neurotoxicity and cell death in developing brain: the role of phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways, overview
role of mitogen-activated protein kinase kinase 4 in cancer, overview. MKK4 is also involved in the immune system and development of B- and T-cells, as well as in cardiac hypertrophy, overview
interaction of ZmMKK1 and ZmMEKK1, a MAP kinase kinase kinase, in vitro
dependent on
subdomain II with an invariable lysine residue is responsible for ATP binding
upon ATP-binding, the transient conformation adopted the configuration of typical kinase folding. In the absence of ATP-binding, the transient state of apo npMAP2K4 may shift to a state of aggregation via non-particular hydrophobic interactions as a result of the exposed hydrophobic residues
Ca2+
elevation of cytosolic Ca2+ by ethylene may stimulate protein phosphatase and MAPKK, which finally activates IPO expression
Cd2+
can partially substitue Mg2+
Co2+
Mg2+
Mn2+
mitogen-activated protein kinase kinase 5, MKK5, is activated in response to salt stress
serine/threonine and tyrosine kinase activities are distinctly influenced by Mg2+ and Mn2+ cofactors. Pfnek3 can undergo further tyrosine autophosphorylation in vitro, with Mn2+ as the preferred metal cofactor
required; required
dependent on, Mg2+ is the physiologic metal ion, other divalent cations are able to support nucleotide binding, but only Mn2+, Co2+, and Cd2+ can substitute Mg2+ in supporting the catalytic activity
highly activating, more effective than Mg2+
1-(2,3-dihydroxypropyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
1-(3-cyanopropyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
1-allyl-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
1-ethyl-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
1-methyl-4-(2-naphthylamino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide
3,4-difluoro-N-(3-{5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3-phenyl-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl}phenyl)-5-hydroxybenzamide
3,4-difluoro-N-{3-[3-(3-fluoro-4-hydroxyphenyl)-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}-5-hydroxybenzamide
3,4-difluoro-N-{3-[5-({2-fluoro-4-[(hydroxymethyl)amino]phenyl}amino)-3-(3-fluoro-4-hydroxyphenyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}-5-hydroxybenzamide
3,4-difluoro-N-{3-[5-{[2-fluoro-4-(formylamino)phenyl]amino}-3-(3-fluoro-4-hydroxyphenyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}-5-hydroxybenzamide
4-(2-fluoro-4-iodoanilino)-1-(2-hydroxyethyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-iodoanilino)-1-(3-hydroxypropyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid
4-(2-fluoro-4-iodoanilino)-1-[2-(2-methoxyethoxy)ethyl]-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-iodoanilino)-6-oxo-1-propyl-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-iodoanilino)-N,1-dimethyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-iodoanilino)-N,N,1-trimethyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-iodoanilino)-N-(3-hydroxypropyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-methylanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(2-fluoro-4-methylsulfanylphenylamino)-1-methyl-6-oxo-1,6-dihydro-3 -pyridinecarboxamide
4-(3,4-dichlorophenylamino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(4-bromo-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(4-bromo-2-fluoroanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(4-bromo-2-fluorophenylamino)-1-methylpyridin-2(1H)-one
selective anthranilic acid type inhibitors, residues K97, I141, M143, F129, V127, I126, L118, F209, V211, and S212 of MEK1/2 are important for interaction with the inhibitor, noncompetitive to ATP, inhibition of ERK phosphorylation by MEK1/2 by the derivatives with IC50 values of 6.8-124 nM, low cytotoxic effects, overview
4-(4-cyano-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(4-ethyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-(4-ethynyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-amino-1-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl]-2-hydroxybutan-1-one
4-[2-fluoro-4-(1,1,2,2,3,3,4,4,4-nonafluorobutyl)anilino]-1-methyl-6-oxo-1,6 -dihydro-3-pyridinecarboxamide
4-[2-fluoro-4-(3-hydroxypropyl)anilino]-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
4-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl]-3-hydroxy-4-oxobutanamide
anthrax lethal toxin
i.e. LeTx, inactivates MKKs, LeTx treatment reduces the levels of phosphorylated extracellular signal-regulated kinase and p38 MAPK in vitro, short treatments with LeTx only modestly affects cell proliferation, sustained treatment markedly reduces cell numbers, LeTx also substantially inhibits the extracellular release of angioproliferative factors including vascular endothelial growth factor, interleukin-8, and basic fibroblast growth factor, overview
a MEK1–2 inhibitor, binds in the allosteric site of MEK1. For A-375 cells, AS-703026 has a growth IC50 of 4 nM
BAY 869766
i.e. RDEA119
suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after mechanical injury in vitro
CH-4987655/RO4987655
a MEK1/2 inhibitor
CH4987655
CI-1040
Cocoa procyanidin B2
procyanidin B2 suppresses TPA-induced phosphorylation of MEK, ERK, and p90RSK in JB6 P+ cells, suppresses JB6 P+ cell transformation by inhibiting mitogen-activated protein kinase kinase, molecular mechanism, overview
Cocoa procyanidins
suppresses JB6 P+ cell transformation by inhibiting mitogen-activated protein kinase kinase, molecular mechanisms of the chemopreventive potential of cocoa and its active ingredients, overview
blocks proliferation of many of the cell lines typically used in testing MEK inhibitors, such as Colo205 and MiaPaca-2
ethyl 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate
GDC0973
GSK1120212
LL-Z1640-2
a MEK1 inhibitor, which shows reasonable MEK inhibition but a very short half-life
MEK162
MIIC
i.e. MEK inhibitor I, the MEK1/2 inhibitor causes NAD(H) reduction, heme oxidation, and decreased oxygen consumption; i.e. MEK inhibitor I, the MEK1/2 inhibitor causes NAD(H) reduction, heme oxidation, and decreased oxygen consumption
N-(3-{3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl}phenyl)-3,4-difluoro-5-hydroxybenzamide
N-(3-{3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl}phenyl)benzamide
N-(3-{3-cyclopropyl-5-[(4-cyclopropyl-2-fluorophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl}phenyl)-2-oxopropanamide
N-(3-{5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3-phenyl-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl}phenyl)-2-oxopropanamide
N-(3-{5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3-phenyl-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl}phenyl)benzamide
N-{3-[3-(3-fluoro-4-hydroxyphenyl)-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}-2-oxopropanamide
N-{3-[5-(cyclopropylmethyl)-3-(3-fluoro-4-hydroxyphenyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}-3,4-difluoro-5-hydroxybenzamide
N-{3-[5-(cyclopropylmethyl)-3-(4-hydroxy-3-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}-3,4-difluoro-5-hydroxybenzamide
N-{3-[5-(cyclopropylmethyl)-3-(4-hydroxyphenyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}-3,4-difluoro-5-hydroxybenzamide
PD0325901
MEK1 inhibitor
a MEK-specific inhibitor
PD184352/CI-1040
a allosteric, non-ATP competitive MEK inhibitor
an orally active MEK1/2 inhibitor, acting as an uncoupler; an orally active MEK1/2 inhibitor, acting as an uncoupler
PD98059
a N-methyl-D-aspartate receptor antagonist, it is neurotoxic to developing brains and results in schizophrenia-like behaviors later in development, it elicites time-dependent inhibition of the MEK/ERK and PI-3K/Akt pathways, overview
RDEA119
refametinib
selumetinib
TAK733
tert-butyl [5-(aminocarbonyl)-4-(2-fluoro-4-iodoanilino)-2-oxo-1(2H)-pyridinyl]acetate
trametinib
XL-518/GDC-0973
selective for MEK1 relative to MEK2
[5-(aminocarbonyl)-4-(2-fluoro-4-iodoanilino)-2-oxo-1(2H)-pyridinyl]acetic acid
ARRY424704, renamed AZD8330
or RO4987655, a non-ATP competitive inhibitor, highly selective for MEK1
MEK-specific inhibitor, enhances antileukemia activity of Mdm2 antagonists in AML cells and p53-mediated transcription-dependent apoptosis. MEK inhibition accumulates p53 into the nucleus in OCIAML-3 cells, but does not affect the nucleoplasmic localization of Mdm2. The inhibitor restricts p21-mediated antiapoptotic mechanisms by repressing p53-dependent induction of p21, which enables Nutlin-3a to induce sufficient apoptosis in G1-phase cells
inhibition of MEK1 with either PD98059 results in a substantial dose-dependent inhibition of SMAD3 promoter activity, reduced SMAD3 protein expression in A549 cells and airway smooth muscle cells after treatment with MEK1 inhibitors; substantial dose-dependent inhibition of SMAD3 promoter activity, 5.8fold reduction, MEK1 inhibition of SMAD3 promoter function is primarily mediated through an Sp1-dependent mechanism
the MEK1/2 inhibitor causes NAD(H) reduction, heme oxidation, and decreased oxygen consumption; the MEK1/2 inhibitor causes NAD(H) reduction, heme oxidation, and decreased oxygen consumption
MAPKK inhibitor, inhibits IPO expression stimulated by staurosporine
inhibitor specific for MEK/ERK activation, granulocyte/macrophage colony number is decreased by ca. 60%
the MEK inhibitor completely blocks adenosine-stimulated corticosterone production
MEK inhibitor, effective dose of 0.05 mM
i.e. AZD6244, potent and highly selective, non-ATP competitive inhibitor of MEK1/2, MEK1 phosphorylation of ERK2. The compound inhibits growth of cell lines
MEK1/2-specific inhibitor, delays, but does not block the passage of synchronized HeLa cells into M phase
cells transiently transfected with two independent sets of siRNAs show significant down-regulation of MKK3 and phosphorylated MKK3
knockdown of MEK, HSCs give rise to Mac-1+ myeloid cells less efficiently than control HSCs
a mitogen-activated protein kinase kinase 1 (MEK1)/MEK2 inhibitor with activity against multiple myeloid cell lines at low nanomolar concentrations, preferential activity among RAS-mutated myeloid malignancies. During clinical oral treatment, most commonly reported treatment-related adverse events are diarrhea, rash, nausea, and increased alanine aminotransferase levels, repeated cycles of trametinib are well tolerated with manageable or reversible toxicities, overview; a mitogen-activated protein kinase kinase 1 (MEK1)/MEK2 inhibitor with activity against multiple myeloid cell lines at low nanomolar concentrations, preferential activity among RAS-mutated myeloid malignancies. During clinical oral treatment, most commonly reported treatment-related adverse events are diarrhea, rash, nausea, and increased alanine aminotransferase levels, repeated cycles of trametinib are well tolerated with manageable or reversible toxicities, overview
inhibition of MEK1 with either UO126 results in a substantial dose-dependent inhibition of SMAD3 promoter activity, reduced SMAD3 protein expression in A549 cells and airway smooth muscle cells after treatment with MEK1 inhibitors; substantial dose-dependent inhibition of SMAD3 promoter activity, 2.3fold reduction, MEK1 inhibition of SMAD3 promoter function is primarily mediated through an Sp1-dependent mechanism
MEK inhibitor
specific MEK inhibitor
potent MEK-1/2 inhibitor, cellular size, DNA fragmentation, nuclear condensation, and the phosphorylated ERK-1 protein products of H9c2 cells treated with Porphyromonas gingivalis medium, are all significantly reduced after pre-administration of U0126
MEK inhibitor, effective dose at 0.1 mM
a specific inhibitor for MEK1/2/ERK1/2
MEK, p38, and IKK inhibitors block TNF-alpha-induced IL-8, IL-6, and GM-CSF secretion and 12z invasion, whereas the PI3K inhibitors do not
stress-induced target of rapamycin complex 1 activation can be blocked by RNAi against mitogen-activated protein kinase kinase 3 and 6
known inhibitor structure screening, and design of specific allosteric MEK1/2 inhibitors with improved pharmacokinetic/pharmacodynamic profiles to be used as alternative cancer medications. Trametinib is used as the lead structure. Molecular docking and binding simulations, thermodynamics, and quantitative structure-activity relationships, allosteric inhibitory site, overview
the MEK enzyme contains a hydrophobic allosteric pocket adjacent to the ATP-binding site which allows for the design of highly selective allosteric inhibitors
design of small molecule MEK1/2 inhibitors to block ERK1/2-mediated signaling and inhibit proliferation. Four structurally distinct MEK1/2 inhibitors acutely affect mitochondrial bioenergetics. The anti-mitochondrial effects of MEK1/2 inhibitors determine the proliferative potential; design of small molecule MEK1/2 inhibitors to block ERK1/2-mediated signaling and inhibit proliferation. Four structurally distinct MEK1/2 inhibitors acutely affect mitochondrial bioenergetics. The anti-mitochondrial effects of MEK1/2 inhibitors determine the proliferative potential
SymRK acts as an inhibitor of SIP2 kinase activity when MPK6 is used as a substrate, suggesting that SymRK may serve as a negative regulator of the SIP2 signaling pathway. SymRK and SIP2 interact with each other but cannot use one another as a substrate for phosphorylation. SymRK can autophosphorylate itself but fails to phosphorylate the kinase-negative SIP2-KR, suggesting that SymRK is neither a potential phosphorylation target nor a kinase source of SIP2
occludin acts as antagonist of the MEK and ERK signaling pathway inducing cell aggregation of pancreatic cancer cells
inactivated by the serine/threonine phosphatase 2A but not by the protein-tyrosine phosphatase 1B
treatment with LY294002, paclitaxel, or serum starvation does not induce apoptosis of wild-type MEF cells
design and synthesis of 4-anilino-5-carboxamido-2-pyridone MEK1 inhibitors using a combination of medicinal chemistry, computational chemistry, and structural elucidation, overview. Binding structure analysis, overview
no MEK inhibition by theobromine
no inhibition of MEK2 by MEK1/ERK1/2-specific inhibitor PD98059
activates
activated by ligation of CD40, the B-cell antigen receptor
induces expression of HA-MEK1
growth factor interleukin-3
MKK3 expression is induced upon Pseudomonas syringae infection
light signals activate the MAP kinase via phosphorylation through MAP kinase kinase
MKKs are activated by phopshorylation through MKKKs, activation mechanism of MKK4 involving MEKK1, overview
activation is induced by epidermal growth factor tyrosine protein kinase and nucelar growth factor tyrosine protein kinase
enzyme is activated by environmental stress and physiological stimuli. In hematopoietic cells, endogenous MKK7 is activated by treatment with the growth factor interleukin-3, or by ligation of CD40, the B-cell antigen receptor, or the receptor for the Fc fragment of immunoglobulin. MKK7 is also activated when cells are exposed to heat, UV irradiation, anisomycin, hyperosmolarity or the pro-inflammatory cytokine tumor necrosis factor-alpha
MEK6 is strongly activated by UV, anisomycin, and osmotic shock
the enzyme is activated in cells treated with tumor necrosis factor-alpha
MEK, ERK-1 and ERK-2 are activated by phosphorylation by B-Raf, the B-Raf mutant V590E activates the enzymes constitutively and independently of Ras, which leads to melanoma cell proliferation
MKKs are activated by phopshorylation through MKKKs, activation mechanism of MKK4 involving MEKK1, overview; MKKs are activated by phopshorylation through MKKKs, overview
dissociation factor DF induces MEK1/2 and ERK1/2 expression
ERK and MEK are activated by phosphorylation, ERK is induced by formalin
the enzyme is activated by phosphorylation through a specific mitogen-activated protein kinase kinase kinase
activation in vivo in response to serum, phosphorylation and activation by the v-Raf protein in vitro
activated by GTP-Cdc42 or GTP-Rac1 in vitro
MEK, ERK-1 and ERK-2 are activated by phosphorylation, tetanus toxin or the C-terminal part of the heavy chain induce phosphorylation of ERK-1 and ERK-2 at Thr202 and Tyr204
MEK and ERK are activated by phosphorylation
neurotrophin induces mitogen-activated protein kinase kinase signaling, which is antagonized by semaphorin 3F, Gab-1, an adaptor protein, is recruited by the TrkA kinase to activate MEK in sympathetic neurons, Gab-1 can reverse semaphorin 3F inhibition of the MEK activation
Pbs2p is activated by MAP kinase kinase kinases Ssk2p and Ssk22p that are under the control of the SLN1-SSK1 two-component osmosensor. Alternatively, Pbs2p is activated by a mechanism that involves the binding of its amino terminal proline-rich motif to the Src homology 3 domain of a putative transmembrane osmosensor Sho1p
enzyme ZmMKK1 interacts with enzyme ZmMEKK1 as determined in yeast two-hybrid assays
Show Disease (1831 entries)
pH 7.0, 25°C
K52R-[ERK2]
K53M-[p38alpha]
Michaelis-Menten kinetics; Michaelis-Menten kinetics
top print hide show all columns Go to IC50 Value Search
IC50 VALUE [mM]
above, cascade IC50
0.00489 - 0.0049
0.000091 - 0.01
cascade IC50; inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
cascade IC50
above, cascade IC50; inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.000004 - 0.000023
0.000425 - 0.005
0.0001 - 0.00063
0.00043 - 0.00254
0.000627 - 1.2
0.000093 - 0.00191
0.0000068 - 0.000124
selective anthranilic acid type inhibitors, residues K97, I141, M143, F129, V127, I126, L118, F209, V211, and S212 of MEK1/2 are important for interaction with the inhibitor, noncompetitive to ATP, inhibition of ERK phosphorylation by MEK1/2 by the deriva
0.000021 - 0.0001
inhibition of MEK1, pH and temperature not specified in the publication
ethyl 4-(2-fuoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate
inhibition of MEK1 phosphorylation of ERK2, pH and temperature not specified in the publication
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
above cascade IC50; colon26 cellular assay
colon26 cellular assay
colon26 cellular assayy
clinical candidate, inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
clinical candidate, colon26 cellular assay
large scale activity assay with recombinant enzyme in a protein chip consisting of a microwell array with protein covalently attached to the wells via a 3-glycidoxypropyltrimethoxysilane crosslinker, overview
assay at; assay at
in vivo assay at
top print hide show all columns Go to Pi Value Search
sequence calculation
i.e. Botryotinia fuckeliana
SwissProt
cv. Tainung 57
cvs. SF43 and Nipponbare
MKK6a; the fish does not possess a MKK3 gene
isolated from a smoke tree, Cotinuscoggygria in Fragrant Hills Park,Beijing
cv. Zhengdan 958
Col-0; the genome contains genes encoding 10 MAPK kinases
MKK1; gene mkk1
gene cpkk1
gene cpkk2; gene cpkk3
663773, 665489, 665990, 679010, 679032, 679153, 681836, 682214, 686415, 688931, 689072, 703169, 705707, 740338, 740419


text:
Agatanghel Savvin (în ; ) este actualul mitropolit de Odesa și Ismail, mitropolie sufragană Mitropoliei Kievului și a Întregii Ucraine, subordonate în prezent Patriarhiei Moscovei și a Întregii Rusii.

Nașteri în 1938
Episcopi ortodocși ruși
Episcopi ortodocși ucraineni


text:
Cuba, Lesotho: 40 years of fruitful ties
June 21, 2019	Lipholo Pheko	400 Views
On June 14, 1979, the Republic of Cuba and the Kingdom of Lesotho decided to formalise their diplomatic relations.
It was an important event in our common history, although in reality the links between both peoples began several centuries ago, in the context of the deep and historic relations that unite Cuba and Africa.
As a consequence of the cruel Atlantic slave trade, nearly 1.3 million Africans arrived in our Island centuries ago.
Their presence had a crucial impact on the formation of the Cuban nation. Africa is part of the very essence of our nation. Cuba is a Latin-African country, deeply proud of its African roots.
Throughout these 40 years of diplomatic ties, our nations have cemented fruitful relations, based on friendship, cooperation and solidarity.
The bilateral cooperation programmes subscribed cover diverse spheres, including health services, education, academic training, physical culture and sports, among others.
Numerous young Basotho professionals have graduated and will continue to graduate in the Cuban universities in multiple specialties, such as medicine, physical culture and sports, agronomy, veterinary, mining, economics, accounting, hydraulic engineering, telecommunications, civil construction, computing, among others.
Just to mention one recent example, on June 5, I had the honor of signing in Maseru, together with the Minister of Health of the Kingdom, Honorable Nkaku Kabi, two important new bilateral cooperation agreements on health.
Under the new agreements, the Cuban Medical Brigade that currently provides services in Lesotho will be significantly expanded and Cuban specialists in general comprehensive medicine, stomatology, as well as other clinical and surgical specialties, prosthetics technicians and specialists on electro medicine, will be deployed in Lesotho shortly.
We will continue to contribute as much as possible to improving the health indicators of the Basotho people.
The systematic political exchange between our countries is also an expression of the permanent consolidation of our bilateral ties. The Minister of Foreign Affairs and International Cooperation of the Kingdom, Honorable Lesego Makgothi, made an official visit to Cuba in October 2018, and a high-level Cuban delegation, led by Inés María Chapman Waugh, Vice President of the Council of State and Ministers, visited the Kingdom last March.
Cuba is deeply grateful for the firm support always received from Lesotho and the rest of the African countries, in the fight against the illegal economic, commercial and financial blockade unilaterally imposed by the United States government against our country for 60 years, support that becomes more relevant to the current upswing in this criminal policy.
Lesotho and Cuba have many reasons to celebrate these first 40 years of fruitful diplomatic relations.
The friendly and fraternal bonds that unite our countries will continue advancing to higher levels, based on the solid common values that bring us together in the search of peace, well-being and prosperity for our peoples and the rest of the peoples of the world.
* Rodolfo Benítez Verson is the Ambassador of Cuba to the Kingdom of Lesotho
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Lipholo Pheko	605 posts
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Fonterra's milk collection across New Zealand for the month of June 2014 reached nine million kgMS, 10% higher than June 2013.
According to its latest update, milk collection continued through June with a small number of farmers milking through winter.
North Island collection in June reached seven million kgMS. This was 13% ahead of June last season. Volumes were up on last season as more farmers continued to milk into winter compared to the previous season.
South Island collection reached two million kgMS, 2% ahead of June last season. Only a small number of South Island farmers provide milk in winter for New Zealand's internal supply.
Milk collection across Australia for the 12 months to 30 June 2014 reached 120 million kgMS, meeting the same level as the previous season, despite being down considerably in the spring.
Milk production in Australia increased in the second half due to more favourable market and pasture growth conditions along with additional farms electing to supply Fonterra. As a result, collection in June was 16% ahead of June last Season.
The table below shows Fonterra milksolids collected in New Zealand for the 2014/15 season and Australia for the 2013/14 season.
According to latest figures from DairyCo, UK daily deliveries for the two weeks ending July 28 averaged 40.7m litres/day, 2.0m litres/day (5.0%) higher than the same period last year.
Daily deliveries for this period were 1.8m (4.7%) higher compared with the three-year average.