Caveolin-1 detergent solubility and association with endothelial nitric oxide synthase is modulated by tyrosine phosphorylation.
Caveolin-1 detergent solubility and association with endothelial nitric oxide synthase is modulated by tyrosine phosphorylation.
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DOI：
10.1006/bbrc.1997.6921
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发表时间：
1997-07
影响因子：
3.1
通讯作者：
V. Venema;R. Zou;H. Ju;M. Marrero;R. Venema
中科院分区：
文献类型：
--
作者：
V. Venema;R. Zou;H. Ju;M. Marrero;R. Venema
小窝蛋白-1和内皮型一氧化氮合酶（eNOS）在内皮小窝内相关。我们以前已经表明，eNOS易位到洗涤剂不溶性，细胞骨架部分的牛主动脉内皮细胞（BAEC）在缓激肽（BK）刺激或酪氨酸磷酸酶抑制。在本研究中，我们研究了小窝蛋白-1是否同样易位在这些或其他刺激。BAEC暴露于eNOS激活激动剂、BK、组胺或ATP会导致洗涤剂不溶性小窝蛋白-1的量短暂增加。不溶性的增加被酪氨酸激酶抑制剂阻断，并被酪氨酸磷酸酶抑制剂有效模拟。增加的不溶性伴随着小窝蛋白-1与eNOS的增加的关联和eNOS催化活性的抑制。因此，内皮细胞中eNOS的激动剂激活似乎涉及eNOS与小窝蛋白-1相互作用中的酪氨酸磷酸化依赖性变化。eNOS与小窝蛋白-1的相互作用的增加可能使酶在其被Ca 2 +/钙调蛋白激活后失活。
Caveolin-1 and endothelial nitric oxide synthase (eNOS) are associated within endothelial caveolae. We have shown previously that eNOS is translocated to the detergent-insoluble, cytoskeletal fraction of bovine aortic endothelial cells (BAEC) in response to bradykinin (BK)-stimulation or tyrosine phosphatase inhibition. In the present study, we have examined whether caveolin-1 is similarly translocated in response to these or other stimuli. Exposure of BAEC to the eNOS-activating agonists, BK, histamine, or ATP produces transient increases in the amounts of detergent-insoluble caveolin-1. Increases in insolubility are blocked by tyrosine kinase inhibitors and are potently mimicked by tyrosine phosphatase inhibitors. Increased insolubility is accompanied by an increased association of caveolin-1 with eNOS and inhibition of eNOS catalytic activity. Agonist-activation of eNOS in endothelial cells thus appears to involve tyrosine phosphorylation-dependent changes in the interaction of eNOS with caveolin-1. Increased interaction of eNOS with caveolin-1 may deactivate the enzyme subsequent to its activation by Ca2+/calmodulin.