Activation of Ras and Other Signaling Pathways by Receptor Tyrosine Kinases

Abstract

Polypeptide growth factors such as epidermal growth factor (EGF), fibroblast growth factor (FGF), or platelet-derived growth factor (PDGF) play an important role in the control of cell growth and differentiation. Peptide growth factors mediate their diverse biological responses by binding to and activating cell-surface receptors with intrinsic protein tyrosine kinase activity (Schlessinger and Ullrich 1992). Growth factor binding to the extracellular domains of their surface receptors induces receptor dimerization. Receptor dimerization is responsible for activation of the intrinsic protein tyrosine kinase activity and for autophosphorylation: Both processes are mediated by an intermolecular process (Schlessinger 1988). Receptor autophosphorylation functions as a molecular switch. Autophosphorylation of receptors such as insulin, insulin-like growth factor 1 (IGF1), or FGF receptors maintains their intrinsic protein tyrosine kinases in an active state. Autophosphorylation sites of other receptors such as EGF receptor compete with exogenous substrates for the catalytic domain. In the case of the EGF receptor,...