期刊
EUROPEAN JOURNAL OF BIOCHEMISTRY
卷 268, 期 15, 页码 4158-4168出版社
BLACKWELL SCIENCE LTD
DOI: 10.1046/j.1432-1327.2001.02327.x
关键词
signal transduction; tyrosine phosphorylation; tyrosine kinase receptor; insulin receptor substrate; phosphatidylinositol 3-kinase
In accordance with our recent results obtained with cultured rat hepatocytes [Fujioka, T. & Ui. M. (2001) Eur J. Biochem. 268, 25-34], epidermal growth factor (EGF) gave rise to transient tyrosine phosphorylation of insulin receptor substrates (IRS-1 and IRS-2), thereby activating the bound phosphatidylinositol 3-kinase in human epidermoid carcinoma A431 cells normally abundant in EGF receptors (EGFR) and Chinese hamster ovary (CHO) cells transfected with full-length EGFR. These actions of EGF, although much smaller in magnitude than those of insulin or IGF-I in the same cells. were accompanied by tyrosine phosphorylation of EGFR rather than insulin or IGF-I receptors, never observed in wild-type CHO cells expressing no EGFR, and totally inhibited by an inhibitor of EGFR kinase, AG1478, that was without effect on insulin or IGF-I actions. Recombinant IRS-1 was phosphorylated on tyrosines upon incubation with purified EGFR from A431 cells and P-32-labeled ATR When CHO cells were transfected with C-terminal truncated EGFR lacking three NPXY motifs responsible for direct binding to phosphotyrosine-binding domains of IRSs, no effect of EGF could be observed. We suggest that tyrosine phosphorylation of IRS-1 or IRS-2 could mediate EGFR-induced activation of phosphatidylinositol 3-kinase in mammalian cells.
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