Protein Kinases are receptor type or non-receptor type proteins, which transfer the terminal phosphate of ATP to aminoacid residues, such as tyrosine, threonine, serine residues, of proteins, thereby activating or inactivating signal transduction pathways. These proteins are known to be involved in many cellular mechanisms, which in case of disruption, lead to disorders such as abnormal cell proliferation and migration as well as inflammation.
As of today, there are over 500 known Protein kinases. Included are the well-known Abl, Akt1, Akt2, Akt3, ALK, Alk5, A-Raf, Axl, B-Raf, Brk, Btk, Cdk2, Cdk4, Cdk5, Cdk6, CHK1, c-Raf-1, Csk, EGFR, EphA1, EphA2, EphB2, EphB4, Erk2, Fak, Fes, Fer, FGFR1, FGFR2, FGFR3, FGFR4, Flt-3, Fms, Frk, Fyn, Gsk3α, Gsk3β, HCK, Her2/Erbb2, Her4/Erbb4, IGF1R, IKK beta, Irak4, Itk, Jak1, Jak2, Jak3, Jnk1, Jnk2, Jnk3, KDR, Kit, Lck, Lyn, MAP2K1, MAP2K2, MAP4K4, MAPKAPK2, Met, Mer, MNK1, MLK1, mTOR, p38, PDGFRα, PDGFRβ, PDPK1, PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, Pim1, Pim2, Pim3, PKC alpha, PKC beta, PKC theta, Plk1, Pyk2, Ret, ROCK1, ROCK2, RON, Src, Stk6, Syk, TEC, Tie2, TrkA, TrkB, Tyk2, VEGFR1/Flt-1, VEGFR2/Kdr, VEGFR3/Flt-4, Yes, and Zap70.
Spleen tyrosine kinase (Syk), an intracellular protein tyrosine kinase, is a key mediator of immunoreceptor signalling in a host of inflammatory cells including B cells, mast cells, macrophages, and neutrophils (Wong Br et al (2004), Expert Opin. Investig. Drugs, 13, 743-762). Syk is also widely expressed in nonhematopoietic cells like fibroblasts, breast cancer cells, colonic carcinoma cells, hepatocytes, neuronal cells, and vascular endothelial cells (Okamura S et al (1999), Onco. Res. 11, 281-285). Originally, Syk was thought to function primarily in signaling of immunoreceptors such as Fc receptor (FcR) and B cell receptor (BCR). However, recent studies demonstrated the crucial role of Syk in the cell signaling of diverse cellular stimuli including IL-1, tumor necrosis factor-α (TNFα), lipopolysaccharide, and β1-integrin (Yamada T et al (2001), J. Immunol., 167, 283-288). For instance, Syk can be activated by TNFα, resulting in MAPK phosphorylation and NF-κB translocation in hematopoietic cell lines (Takada Y and Aggarwal BB (2004), J. Immunol., 173, 1066-1077). IL-1-induced chemokine production in fibroblasts of nasal polyps is also mediated by Syk activation (Yamada T et al (2001), J. Immunol., 167, 283-288). Syk has emerged as a potential therapeutic target for treatment of allergic and autoimmune disorders.