Human endothelial Pyk2 is expressed in two isoforms and associates with paxillin and p130Cas
Human endothelial Pyk2 is expressed in two isoforms and associates with paxillin and p130Cas
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DOI：
10.1006/bbrc.2002.6350
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发表时间：
2002-02-08
影响因子：
3.1
通讯作者：
Wheeler-Jones, CPD
中科院分区：
文献类型：
--
作者：
Keogh, RJ;Houliston, RA;Wheeler-Jones, CPD
富含脯氨酸的激酶2（Pyk 2）是属于粘着斑激酶家族的非受体酪氨酸激酶。许多刺激可以启动Pyk 2的磷酸化和激活，但其特异性激活剂和下游靶点在很大程度上仍然是未知的，并且对Pyk 2在内皮细胞中的激活机制或作用知之甚少。在人脐静脉内皮细胞（HUVEC）中，我们发现（1）Pyk 2在酪氨酸残基402、580和881处磷酸化，以响应G蛋白偶联受体激动剂（GPCA）、血管内皮生长因子和细胞因子白细胞介素-Ia的刺激;（2）HUVEC表达Pyk 2的两种亚型的mRNA，它们似乎不受GPCA、生长因子或细胞因子的转录调控;和（3）Pyk 2定位于胞质溶胶，并通过其C-末端与细胞骨架蛋白桩蛋白和接头分子p130 Cas在磷酸化非依赖性相互作用中缔合。这些结果表明，Pyk 2被迅速激活，并与结构和衔接蛋白，这表明它是一个重要的激酶参与介导的急性反应的内皮。(C)2002 Elsevier Science（美国）。
Proline-rich kinase 2 (Pyk2) is a non-receptor tyrosine kinase belonging to the focal adhesion kinase family. Many stimuli can initiate phosphorylation and activation of Pyk2 but its specific activators and downstream targets are still largely unidentified and little is known of the mechanisms or role of Pyk2 activation in endothelial cells. In human umbilical vein endothelial cells (HUVEC), we show that (1) Pyk2 is phosphorylated on tyrosine residues 402, 580, and 881 in response to stimulation with G-protein-coupled receptor agonists (GPCAs), vascular endothelial growth factor, and the cytokine interleukin-la; (2) HUVEC express mRNA for two isoforms of Pyk2 which do not appear to be regulated transcriptionally by GPCAs, growth factors, or cytokines; and (3) Pyk2 is localised to the cytosol and associates through its C-terminus with the cytoskeletal protein paxillin and the adapter molecule p130Cas in phosphorylation-independent interactions. These results demonstrate that Pyk2 is rapidly activated and associates with structural and adapter proteins suggesting that it is an important kinase involved in mediating acute responses in endothelium. (C) 2002 Elsevier Science (USA).