Arachidonate-induced tyrosine phosphorylation of epidermal growth factor receptor and Shc-Grb2-Sos association.
Arachidonate-induced tyrosine phosphorylation of epidermal growth factor receptor and Shc-Grb2-Sos association.
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花生四烯酸诱导表皮生长因子受体酪氨酸磷酸化和 Shc-Grb2-Sos 关联。
DOI：
10.1161/01.hyp.32.6.1089
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Douglas,JG
中科院分区：
文献类型：
--
作者：
Dulin,NO;Sorokin,A;Douglas,JG
研究了兔肾近端小管上皮细胞中重要的脂质第二信使花生四烯酸（AA）对蛋白酪氨酸的磷酸化作用。AA刺激了一些蛋白的酪氨酸磷酸化，估计分子量为42、44、52、56、85和170/180 kDa。磷酸化蛋白pp44和pp42被鉴定为丝裂原活化蛋白激酶（MAPK）的2种异构体。AA对MAPK的磷酸化反应是短暂的，剂量依赖性的，并伴随着其活性的增加。aa在RTE细胞中诱导MAPK活化的机制与蛋白激酶c无关，与衔接蛋白Shc的酪氨酸磷酸化及其与Grb2-Sos复合物的关联有关。此外，AA刺激RTE细胞导致表皮生长因子（EGF）受体的显著磷酸化及其与Shc的关联。AA对EGF受体磷酸化、与Shc的关联以及MAPK激活的影响与1 ng/mL EGF的作用相似。Tyrphostin AG1478是一种特异性的EGF受体酪氨酸激酶活性抑制剂，可以完全阻断AA和EGF对MAPK磷酸化的作用，但不能阻断phorbol酯对MAPK磷酸化的作用。这些数据表明，在肾小管上皮细胞中，aa诱导的MAPK激活机制涉及EGF受体酪氨酸磷酸化及其与Shc和Grb2-Sos复合物的关联。鉴于AA在G蛋白偶联受体（gpcr）信号传导中的关键作用，这些观察结果为gpcr与磷脂酶和酪氨酸激酶受体信号级联之间的串扰提供了一种机制。
—Protein tyrosine phosphorylation induced by arachidonic acid (AA), an important lipid second messenger, was investigated in rabbit renal proximal tubule epithelial cells. AA stimulated tyrosine phosphorylation of a number of proteins with estimated molecular weights of 42, 44, 52, 56, 85, and 170/180 kDa. The phosphoproteins pp44 and pp42 were identified as 2 isoforms of mitogen-activated protein kinase (MAPK). Phosphorylation of MAPK in response to AA was transient, dose-dependent, and accompanied by an increase in its activity. The mechanism of AA-induced MAPK activation in RTE cells was protein kinase C–independent and involved tyrosine phosphorylation of adaptor protein Shc and its association with Grb2-Sos complex. Moreover, stimulation of RTE cells with AA resulted in significant phosphorylation of epidermal growth factor (EGF) receptor and its association with Shc. The effect of AA on EGF receptor phosphorylation, its association with Shc, and MAPK activation was similar to the effect of 1 ng/mL EGF. Tyrphostin AG1478, a specific inhibitor of EGF receptor tyrosine kinase activity, completely blocked the effects of AA and EGF but not phorbol ester on MAPK phosphorylation. These data suggest that in renal tubular epithelial cells, the mechanism of AA-induced MAPK activation involves tyrosine phosphorylation of EGF receptor and its association with Shc and Grb2-Sos complex. Given the critical role of AA in signaling linked to G protein–coupled receptors (GPCRs), these observations provide a mechanism for cross talk between GPCRs linked to phospholipases and the tyrosine kinase receptor signaling cascades.