Fig. 7.3 Assembly of signaling complexes is mediated by scaffold and adaptor proteins. assembly of signaling complexes is an important aspect of signal transduction. This is often achieved through scaffold and adaptor proteins. in general, scaffolds have numerous sites of phosphorylation that function to bring many different signaling proteins together (top panel). Scaffolds may also function to promote membrane localization, to bring enzymes into close proximity with their substrates, and to induce conformational changes in proteins that regulate their functions. an adaptor protein functions to bring two different proteins together (bottom panel). When erythropoietin (epo) binds to its receptor, associated tyrosine kinases phosphorylate (red dots) sites on the epo receptor cytoplasmic domain, generating binding sites for the Sh2 domain of an adaptor protein. The adaptor protein (green) shown here contains two Sh3 domains in addition to an Sh2 domain. With the Sh3 domains it can, for example, bind proline-rich sites on an intracellular signaling molecule (yellow).
Over time, the small G protein hydrolyzes the GTP to GDP and becomes inactive, a process that is accelerated by GAPs The GTP-bound small G protein is the active effector molecule Signaling activates guanine-nucleotide exchange factors (GEFs) such as Sos, which increase the rate of exchange of GDP for GTP In the resting state, small G proteins are bound to GDP and are inactive GTP GDP:Ras GDP:Ras GTP:Ras active Ras GEF
Fig. 7.4 Small G proteins are switched from inactive to active states by guanine-nucleotide exchange factors (GEFs) and the binding of GTP. Ras is a small GTp-binding protein with intrinsic GTpase activity. in its resting state, Ras is bound to Gdp. Receptor signaling activates guanine-nucleotide exchange factors (Gefs), such as Sos, which can bind to small G proteins such as Ras and increase the rate of exchange of Gdp for GTp (center panels). The GTp-bound form of Ras can then bind to a large number of effectors, recruiting them to the membrane. over time, the intrinsic GTpase activity of Ras will result in the hydrolysis of GTp to Gdp. GTpase-activating proteins (Gaps) can accelerate the hydrolysis of GTp to Gdp, thus shutting off the signal more rapidly.
7-3 Small G proteins act as molecular switches in many different signaling pathways.
Monomeric GTP-binding proteins known as small G proteins or small GTPases are important in the signaling pathways leading from many tyrosine kinase-associated receptors. The small GTPases are distinct from the larger heterotrimeric G proteins associated with G-protein-coupled receptors such as the chemokine receptors discussed in Chapter 3. The superfamily of small GTPases comprises more than 100 different proteins, and many are important in lymphocyte signaling. One of these, Ras, is involved in many pathways leading to cell proliferation. Other small GTPases include Rac, Rho, and Cdc42, which control changes in the actin cytoskeleton caused by signals received through the T-cell receptor or B-cell receptor. We will describe their actions in more detail in Section 7-19.