Role of c-Src tyrosine kinase in EGF-induced mitogenesis

摘要: c-Src, the prototype of cytoplasmic, membrane-associated,non-receptor tyrosine kinases, is a co-transducer mitogenic signals emanating from number kinase polypeptide growth factor receptors. Examples such receptors include those that bind platelet-derived (PDGF), colony stimulating factor-1 (CSF-1), and epidermal (EGF). Investigations into mechanisms by which c-Src contributes to receptor signaling suggest interactions between two proteins are bidirectional, i.e., can bind, phosphorylate, activate receptor, vice versa. The consequences these appear be enhanced phosphorylation specific substrates. Delineating cellular substrates determining on function goals current investigations. Utilizing murine C3H10T fibroblast model, in panel wild type mutant c-Src/EGF overexpressors has been studied for temporal spatial second messenger responses EGF, distinctions EGF effects substrate beginning emerge. In 10T preferred almost exclusively comprised molecules associate with actin cytoskeleton or focal adhesions, as cortactin, p190RhoGAP, p130CAS, while itself, SHC, phospholipase C-gamma p62DOK. While major pathway thought proceed directly (through SHC/GRB2/SOS/Ras/Raf/MEK/MAPkinase/Elk1), more evidence accumulating involved regulating (such substrates) also participate mitogenesis, either unique transducers and/or monitors anti-apoptotic conditions (substratum attachment). How may contribute response through association its discussed. Cellular Src (c-Src), family intracellular membrane-associated required mitogenesis initiated multiple receptors, including (EGF), basic (bFGF). C-Src overexpressed activated many same human carcinomas overexpress members (EGFR) family, suggesting types kinases cooperate during genesis tumors. This review focuses role EGF-dependent tumorigenesis, identification substrates, their functions, phosphorylations functions. A synopsis other systems included comparative purposes.