title: Requirement of autophosphorylated tyrosine 992 of EGF receptor and its docking protein phospholipase C gamma 1 for membrane ruffle formation.
abstract: Stimulation of the epidermal growth factor receptor (EGFR) produces membrane ruffles through the small G protein Rac1; however, the signaling pathway from EGFR to Rac1 has not yet been clarified. Here, we show that autophosphorylation of EGFR at tyrosine 992 is required for EGF-induced membrane ruffle formation in CHO cells. Signaling from the autophosphorylated tyrosine 992 appears to be mediated by phospholipase C (PLC) gamma 1. Furthermore, activation of Rac1 by EGF is inhibited by a PLC inhibitor. These results, taken together, suggest that autophosphorylation of EGFR at tyrosine 992 and the subsequent PLC gamma 1 activation transduce the signal to Rac1 to induce membrane ruffle formation.
authors.affiliation: Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nogami
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Okabayashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kido
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Maehama
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kanaho
mesh_terms: D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure; D006224:Cricetinae; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000737:chemistry* / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051966:Phospholipase C gamma; D010766:Phosphorylation; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D020830:rac1 GTP-Binding Protein