The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions.
Ligand-induced activation of receptor tyrosine kinases (RTK) results in the initiation of diverse cellular pathways, including proliferation, differentiation and cell migration. The ErbB family of RTKs represents a model for signal diversification through the formation of homo- and heterodimeric receptor complexes. Each dimeric receptor complex will initiate a distinct signaling pathway by recruiting a different set of Src homology 2- (SH2-) containing effector proteins. Further complexity is added due to the existence of an oncogenic receptor that enhances and stabilizes dimerization but has no ligand (ErbB-2), and a receptor that can recruit novel SH-2-containing proteins, but is itself devoid of kinase activity (ErbB-3). The resulting signaling network has important implications for embryonic development and malignant transformation.
Alroy
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I
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
Yarden
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Y
D000818:Animals; D002471:Cell Transformation, Neoplastic; D005314:Embryonic and Fetal Development / Q000502:physiology; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D015398:Signal Transduction
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D008024:Ligands; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587689:ERBB4 protein, human