ErbB receptors: directing key signaling networks throughout life.
The epidermal growth factor (EGF)-related peptides bind the ErbB receptors, inducing the formation of different homo- and heterodimers. Receptor dimerization promotes activation of the intrinsic kinase, leading to phosphorylation of specific tyrosines located in the ErbB's cytoplasmic region. These phosphorylated residues serve as docking sites for a variety of signaling molecules whose recruitment stimulates intracellular signaling cascades, which ultimately control diverse genetic programs. Particular ligand-receptor complexes have essential roles in embryonic development as well as in the adult. Finally, ErbB receptors are being pursued as therapeutic targets because aberrant ErbB activity has been observed in many human cancers. In this review, we discuss these data in more detail, illustrating the importance of tightly regulated ErbB signaling throughout life.
Holbro
Thomas
T
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland. holbro@fmi.ch
Hynes
Nancy E
NE
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology; D020893:Receptor, ErbB-3 / Q000378:metabolism* / Q000502:physiology; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000502:physiology*
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587689:ERBB4 protein, human