Requirement of autophosphorylated tyrosine 992 of EGF receptor and its docking protein phospholipase C gamma 1 for membrane ruffle formation.
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.
Nogami
Masahiro
M
Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Yamazaki
Masakazu
M
Watanabe
Hiroshi
H
Okabayashi
Yoshinori
Y
Kido
Yoshiaki
Y
Kasuga
Masato
M
Sasaki
Takehiko
T
Maehama
Tomohiko
T
Kanaho
Yasunori
Y
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
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