Activation of Ras by receptor tyrosine kinases.

摘要: Ras, a small GTP-binding protein, is an important component of the signal transduction pathway used by growth factors to initiate cell and differentiation. Cell activation with such as epidermal factor (EGF) induces Ras move from inactive GDP-bound state active GTP-bound state. Recently, combination genetic biochemical studies has resulted in elucidation signaling that leads receptors Ras. After binding EGF, EGF receptor tyrosine kinase activated, leading autophosphorylation on multiple residues. Signaling proteins Src homology 2 (SH2) domains then bind these tyrosine-phosphorylated residues, initiating cascades. One SH2 domain proteins, Grb2, exists cytoplasm preformed complex second Son Sevenless (Sos), which can catalyze GTP/GDP exchange. stimulation, phosphorylated binds Grb2/Sos complex, translocating it plasma membrane. This translocation thought bring Sos into close proximity In contrast, insulin does not Grb2 directly but rather phosphorylation two substrate-1 Shc, complex. Once proceeds stimulate cascade protein kinases are myriad responses.