Protein kinase C beta regulates heterologous desensitization of thrombin receptor (PAR-1) in endothelial cells.
Protein kinase C beta regulates heterologous desensitization of thrombin receptor (PAR-1) in endothelial cells.
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蛋白激酶 C beta 调节内皮细胞中凝血酶受体 (PAR-1) 的异源脱敏。
DOI：
10.1152/ajpcell.1998.274.2.c387
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Malik,AB
中科院分区：
文献类型：
--
作者：
Yan,W;Tiruppathi,C;Lum,H;Qiao,R;Malik,AB
We studied the effects of protein kinase C (PKC) activation on endothelial cell surface expression and function of the proteolytically activated thrombin receptor 1 (PAR-1). Cell surface PAR-1 expression was assessed by immunofluorescence (using anti-PAR-1 monoclonal antibody), and receptor activation was assessed by measuring increases in cytosolic Ca2+concentration in human dermal microvascular endothelial cells (HMEC) exposed to α-thrombin or phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). Immunofluorescence showed that thrombin and TPA reduced the cell surface expression of PAR-1. Prior exposure of HMEC to thrombin for 5 min desensitized the cells to thrombin, indicating homologous PAR-1 desensitization. In contrast, prior activation of PKC with TPA produced desensitization to thrombin and histamine, indicating heterologous PAR-1 desensitization. Treatment of cells with staurosporine, a PKC inhibitor, fully prevented heterologous desensitization, whereas thrombin-induced homologous desensitization persisted. Depletion of PKCβ isozymes (PKCβIand PKCβII) by transducing cells with antisense cDNA of PKCβIprevented the TPA-induced decrease in cell surface PAR-1 expression and restored ∼60% of the cytosolic Ca2+signal in response to thrombin. In contrast, depletion of PKCβ isozymes did not affect the loss of cell surface PAR-1 and induction of homologous PAR-1 desensitization by thrombin. Therefore, homologous PAR-1 desensitization by thrombin occurs independently of PKCβ isozymes, whereas the PKCβ-activated pathway is important in signaling heterologous PAR-1 desensitization in endothelial cells.
