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

FEBS Letters

Kasuga, Masato³  Kido, Yoshiaki³  Nogami, Masahiro¹  Yamazaki, Masakazu²  Kanaho, Yasunori¹  Maehama, Tomohiko¹  Watanabe, Hiroshi¹  Okabayashi, Yoshinori³  Sasaki, Takehiko¹ 

[1] Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan;Neuronal Circuit Mechanisms Research Group, Brain Science Institute, RIKEN, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan;Second Department of Internal Medicine, Kobe University School of Medicine, Chuo-ku, Kobe 650-0017, Japan

关键词: Epidermal growth factor receptor;    Tyrosine phosphorylation;    Phospholipase Cγ1;    Membrane ruffle;    Rac1;    CHO cell;    ARF;    ADP-ribosylation factor;    CHO;    Chinese hamster ovary;    DAG;    diacylglycerol;    EGF;    epidermal growth factor;    EGFR;    EGF receptor;    ERK;    extracellular signal-regulated kinase;    HA;    hemagglutinin;    PI(4;    5)P2;    phosphatidylinositol 4;    5-bisphosphate;    PI(4)P;    phosphatidylinositol 4-phosphate;    PKC;    protein kinase C;    PLCγ1;    phospholipase Cγ1;    SH2;    Src homology domain 2;    TPA;    12-O-tetradecanoylphorbol 13-acetate;   

DOI  :  10.1016/S0014-5793(03)00013-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown