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Bradykinin Stimulates the Tyrosine Phosphorylation and Bradykinin 62 Receptor Association of Phospholipase Cyl in Vascular Endothelial Cells

机译:BRADYKININ刺激血管内皮细胞中磷脂脂酶酮的酪氨酸磷酸化和Bradykinin 62受体结合

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An early event in bradykinin (BK.) B2 receptor signal transduction is activation of phosphoinositide-specific phospholipase C (PLC). Two alternate mechanisms of PLC activation have been reported consisting of either direct allosteric activation of PLCp isoforms by G-proteins or tyrosine phosphorylation and consequent activation of PLCgamma isoforms. Because the B2 receptor is a G-protein-coupled receptor, it has been assumed that the receptor signals exclusively or predominately through the p isoforms of PLC. hi the present study, however, we have found that BK stimulation of IP3 production and the Ca~(2+) signal in cultured endothelial cells is dependent on tyrosine phosphorylation. We have found further that stimulation of B2 receptors in these cells is accompanied by a transient tyrosine phosphorylation of PLCgammal. Phosphorylation is temporally correlated with increased IP3 production and association of PLCgammal with the C-terminal intracellular domain of the B2 receptor. The B2 receptor can thus physically associate with intracellular proteins other than G-proteins. Furthermore, it appears that activation of PLCy isoforms, rather than PLCp isoforms, may be primarily responsible for BK-stimulated IP3 generation in endothelial cells.
机译:Bradykinin(BK.)B2受体信号转导的早期事件是磷酸阳性特异性磷脂酶C(PLC)的活化。据报道,PLC活化的两种替代机制由G蛋白或酪氨酸磷酸化的PLCP同种型的直接变构激活组成,并随后激活Plcγ同种型。因为B2受体是G蛋白偶联受体,所以已经假设了专用或主要通过PLC的P同种型的受体信号。然而,在本研究中,我们发现,培养内皮细胞中的IP3生产和Ca〜(2+)信号的BK刺激取决于酪氨酸磷酸化。我们发现这些细胞中B2受体的刺激伴有Plcγ的瞬时酪氨酸磷酸化。与B2受体的C末端细胞内结构域的IP3生产和Plcamamp的增加的IP3生产和嗜型缔合的磷酸化时间相关。因此,B2受体可以与除G-蛋白以外的细胞内蛋白物理缔合。此外,似乎具有Plcy同种型的激活,而不是PLCP同种型,可以主要负责内皮细胞中的BK刺激的IP3产生。

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