title: Molecular requirements for the effect of neuregulin on cell spreading, motility and colony organization.
abstract: Neuregulin can trigger morphogenetic signals in cells both in vivo and in culture through the activation of receptors from the ErbB family. We have ectopically expressed various ErbB-receptors in 32D myeloid cells lacking endogenous ErbB-proteins, and in CHO cells, which express only ErbB-2. We show here that activation of ErbB-3/ErbB-2 heterodimeric receptors triggers PI3-kinase-dependent lamellipodia formation and spreading, while individual ErbB-receptor homodimers as well as ErbB-3/ErbB-1 heterodimers are much less effective. CHO cells expressing ErB-3/ErbB-2 together with N-cadherin, an adhesion receptor, form epithelioid colonies. Neuregulin activates cell motility leading to transition of these colonies into ring-shaped multicellular arrays, similar to those induced by neuregulin in epithelial cells of different types (Chausovsky et al., 1998). This process requires both PI3-kinase and MAP kinase kinase activity and depends on coordinated changes in the actin- and microtubule-based cytoskeleton. Transactivation of ErbB-2 is not sufficient for the activation of cell motility and ring formation, and the C-terminal domain of ErbB-3 bearing the docking sites for the p85 subunit of PI3-kinase is essential for these morphogenetic effects. Thus, ErbB-3 in conjunction with ErbB-2 mediates, via its C-terminal domain, cytoskeletal and adhesion alterations which activate cell spreading and motility, leading to the formation of complex structures such as multicellular rings. Oncogene (2000) 19, 878 - 888.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Chausovsky
authors.forename: H
authors.initials: H
authors.lastname: Waterman
authors.forename: M
authors.initials: M
authors.lastname: Elbaum
authors.forename: Y
authors.initials: Y
authors.lastname: Yarden
authors.forename: B
authors.initials: B
authors.lastname: Geiger
authors.forename: A D
authors.initials: AD
authors.lastname: Bershadsky
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D006224:Cricetinae; D003599:Cytoskeleton / Q000502:physiology; D019281:Dimerization; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D009024:Morphogenesis; D020880:Neuregulins / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D020893:Receptor, ErbB-3 / Q000502:physiology; D014162:Transfection
chemical_list: D020880:Neuregulins; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3