Requirement of autophosphorylated tyrosine 992 of EGF receptor and its docking protein phospholipase Cγ1 for membrane ruffle formation

• Published in: FEBS letters 2003-02, Vol.536 (1), p.71-76
• Main Authors: Nogami, Masahiro, Yamazaki, Masakazu, Watanabe, Hiroshi, Okabayashi, Yoshinori, Kido, Yoshiaki, Kasuga, Masato, Sasaki, Takehiko, Maehama, Tomohiko, Kanaho, Yasunori
• Format: Article
• Language: English
• Subjects: ARF, ADP-ribosylation factor; CHO cell; CHO, Chinese hamster ovary; DAG, diacylglycerol; EGF, epidermal growth factor; EGFR, EGF receptor; Epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; HA, hemagglutinin; Membrane ruffle; Phospholipase Cγ1; PI(4,5)P2, phosphatidylinositol 4,5-bisphosphate; PIP, phosphatidylinositol 4-phosphate; PKC, protein kinase C; PLCγ1, phospholipase Cγ1; Rac1; SH2, Src homology domain 2; TPA, 12-O-tetradecanoylphorbol 13-acetate; Tyrosine phosphorylation
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(03)00013-9

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) γ1. 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 PLCγ1 activation transduce the signal to Rac1 to induce membrane ruffle formation.