首页> 外文期刊>American Journal of Physiology >A role for PYK2 in regulation of ERK1/2 MAP kinases and PI 3-kinase by ANG II in vascular smooth muscle.
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A role for PYK2 in regulation of ERK1/2 MAP kinases and PI 3-kinase by ANG II in vascular smooth muscle.

机译:PYK2在血管平滑肌中由ANG II调节ERK1 / 2 MAP激酶和PI 3-激酶的作用。

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摘要

Abnormal vascular smooth muscle cell (VSMC) growth plays a key role in the pathogenesis of hypertension and atherosclerosis. Angiotensin II (ANG II) elicits a hypertrophic growth response characterized by an increase in protein synthesis without cell proliferation. The present study investigated the role of the nonreceptor tyrosine kinase PYK2 in the regulation of ANG II-induced signaling pathways that mediate VSMC growth. Using coimmunoprecipitation analysis, the role of PYK2 as an upstream regulator of both extracellular signal-related kinase (ERK) 1/2 mitogen-activated protein kinase and phosphatidylinositol 3-kinase (PI 3-kinase) pathways was examined in cultured rat aortic VSMC. ANG II (100 nM) promoted the formation of a complex between PYK2 and the ERK1/2 regulators Shc and Grb2. ANG II caused a rapid and Ca(2+)-dependent tyrosine phosphorylation of the adapter molecule p130Cas, which coimmunoprecipitated both PYK2 and PI 3-kinase in ANG II-treated VSMC. Complex formation between PI 3-kinase andp130Cas and PYK2 was associated with a rapid phosphorylation of the ribosomal p70(S6) kinase in a Ca(2+)- and tyrosine kinase-dependent manner. These data suggest that PYK2 is an important regulator of multiple signaling pathways involved in ANG II-induced VSMC growth.
机译:异常血管平滑肌细胞(VSMC)的生长在高血压和动脉粥样硬化的发病机理中起着关键作用。血管紧张素II(ANG II)引起肥大性生长反应,其特征是蛋白质合成增加而没有细胞增殖。本研究调查了非受体酪氨酸激酶PYK2在ANG II诱导的介导VSMC生长的信号通路中的作用。使用共免疫沉淀分析,在培养的大鼠主动脉VSMC中检查了PYK2作为细胞外信号相关激酶(ERK)1/2丝裂原活化蛋白激酶和磷脂酰肌醇3-激酶(PI 3-激酶)途径的上游调节剂的作用。 ANG II(100 nM)促进了PYK2与ERK1 / 2调节剂Shc和Grb2之间的复合物的形成。 ANG II引起衔接子分子p130Cas的快速和Ca(2+)依赖的酪氨酸磷酸化,后者在ANG II处理的VSMC中共同免疫沉淀PYK2和PI 3-激酶。 PI 3-激酶和p130Cas和PYK2之间的复杂形成与核糖体p70(S6)激酶以Ca(2+)和酪氨酸激酶依赖性的方式快速磷酸化有关。这些数据表明PYK2是参与ANG II诱导的VSMC生长的多种信号通路的重要调节剂。

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