THE ERBB SIGNALING NETWORK IN EMBRYOGENESIS AND ONCOGENESIS - SIGNAL DIVERSIFICATION THROUGH COMBINATORIAL LIGAND-RECEPTOR INTERACTIONS

Ligand-induced activation of receptor tyrosine kinases (RTK) results i n the initiation of diverse cellular pathways, including proliferation , differentiation and cell migration. The ErbB family of RTKs represen ts a model for signal diversification through the formation of homo- a nd heterodimeric receptor complexes. Each dimeric receptor complex wil l initiate a distinct signaling pathway by recruiting a different set of Src homology 2- (SH2-) containing effector proteins. Further comple xity is added due to the existence of an oncogenic receptor that enhan ces and stabilizes dimerization but has no ligand (ErbB-2), and a rece ptor that can recruit novel SH-2-containing proteins, but is itself de void of kinase activity (ErbB-3). The resulting signaling network has important implications for embryonic development and malignant transfo rmation. (C) 1997 Federation of European Biochemical Societies.