EGF INDUCES TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE C-II - A POTENTIAL MECHANISM FOR EGF RECEPTOR SIGNALING
EGF INDUCES TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE C-II - A POTENTIAL MECHANISM FOR EGF RECEPTOR SIGNALING
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DOI：
10.1016/0092-8674(89)90047-0
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发表时间：
1989-06-30
期刊：
影响因子：
64.5
通讯作者：
SCHLESSINGER, J
中科院分区：
文献类型：
--
作者：
MARGOLIS, B;RHEE, SG;SCHLESSINGER, J
EGF与表达人EGF受体的细胞的结合刺激磷脂酶C-II（PLC-II）的快速酪氨酸磷酸化，如磷酸酪氨酸特异性抗体的免疫印迹分析所示。PLC-II的酪氨酸磷酸化被低生理浓度的EGF（1 nM）刺激，是定量的，并且在37 ℃与50 nM EGF温育30秒后已经达到最大。C.有趣的是，PLC-II特异性抗体能够共免疫沉淀EGF受体和抗体对EGF受体也共免疫沉淀PLC-II。根据该分析，大约1%的EGF受体分子与PLC-II分子相关。酪氨酸蛋白激酶抑制剂TRYPHOSTIN RG 50864阻断EGF依赖的细胞增殖，阻断EGF诱导的PLC-Ⅱ的酪氨酸磷酸化、PLC-Ⅱ与EGF受体的结合以及EGF诱导的Ca ~（2+）释放。因此，EGF诱导的PLC-Ⅱ的酪氨酸磷酸化可能是连接EGF受体的酪氨酸激酶活性和PIP 2水解信号通路的调节事件。
Binding of EGF to cells expressing human EGF receptor stimulated rapid tyrosine phosphorylation of phospholipase C-II (PLC-II), as revealed by immunoblotting analysis with phosphotyrosine-specific antibodies. Tyrosine phosphorylation of PLC-II was stimulated by low physiological concentrations of EGF (1nM), was quantitative, and was already maximal after a 30 sec incubation with 50 nM EGF at 37.degree. C. Interestingly, antibodies specific for PLC-II were able to coimmunoprecipitate the EGF receptor and antibodies against EGF receptor also coimmunoprecipitated PLC-II. According to this analysis, approximately 1% of EGF receptor molecules were associated with PLC-II molecules. The protein tyrosine kinase inhibitor tryphostin RG50864, which blocks EGF-dependent cell proliferation, blocked EGF-induced tyrosine phosphorylation of PLC-II, its association with EGF receptor, and EGF-induced Ca2+ release, Hence, EGF-induced tyrosine phosphorylation of PLC-II may be a regulatory event linking the tyrosine kinase activity of EGF receptor to the PIP2 hydrolysis signaling pathway.