Regulation of calcium-sensitive tyrosine kinase Pyk2 by angiotensin II in endothelial cells - Roles of Yes tyrosine kinase and tyrosine phosphatase SHP-2

作     者：Tang, H Zhao, ZZJ Landon, EJ Inagami, T 

作者机构：Vanderbilt Univ Sch Med Dept Biochem Nashville TN 37232 USA Vanderbilt Univ Sch Med Dept Pharmacol Nashville TN 37232 USA Vanderbilt Univ Sch Med Div Hematol Nashville TN 37232 USA 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：2000年第275卷第12期

页      面：8389-8396页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：NHLBI NIH HHS [HL-58205  HL-57393] Funding Source: Medline 

主　　题：血管紧张素Ⅱ/代谢 内皮 血管/细胞学 内皮 血管/生理学 黏着斑激酶2 细胞内信号肽和蛋白质类 JNK丝裂原活化蛋白激酶类 丝裂原激活蛋白激酶类/代谢 磷酰化 蛋白质结合 蛋白质酪氨酸磷酸酶 非受体1型 蛋白质酪氨酸磷酸酶 非受体11型 蛋白酪氨酸磷酸酶 非受体6型 蛋白质酪氨酸磷酸酶类/代谢 蛋白酪氨酸激酶类/代谢 原癌基因蛋白质类/代谢 原癌基因蛋白质c-fyn 原癌基因蛋白质c-yes 肺静脉/细胞学 受体 血管紧张素 1型 受体 血管紧张素 2型 受体 血管紧张素/代谢 含SH2域蛋白质酪氨酸磷酸酶类 信号传导 酪氨酸/代谢 src族激酶类/代谢 动物 大鼠 

摘      要：Calcium-sensitive tyrosine kinase Pyk2 has been implicated in the regulation of ion channels, cellular adhesion, and mitogenic and hypertrophic reactions. In this study, we have investigated the regulation of Pyk2 by angiotensin II (Ang II) in pulmonary vein endothelial cells. We found that the Ang II-induced tyrosine phosphorylation of Pyk2, which requires the activity of Src family kinase, was specifically regulated by the Src family kinase member, Yes kinase, Moreover, we identified for the first time the constitutive association of Pyk2 with an Src homology 2 (SH2) domain-containing tyrosine phosphatase SHP-2. SHP-2 interacts with Pyk2 through a region other than its SH2 domains. Pyk2 can be dephosphorylated in vitro in SHP-2 immunoprecipitates and in intact cells expressing an NH, terminus-truncated form of SHP-2, which lacks the two SH2 domains but has an enhanced phosphatase activity. Ang II activates the endogenous SHP-2, Finally, the SHP-2-mediated dephosphorylation of Pyk2 correlates with the negative effect of SHP-2 on the Ang II-induced activation of extracellular signal-regulated kinase and c-Jun NH2-terminal kinase. Thus, the balance of Pyk2 tyrosine phosphorylation in response to Ang II is controlled by Yes kinase and by a tyrosine phosphatase SHP-2 in endothelial cells.