窖蛋白-2 的 N 端酪氨酸磷酸化使转化生长因子-β在血管内皮细胞中的抗增殖作用失效。
N-terminal tyrosine phosphorylation of caveolin-2 negates anti-proliferative effect of transforming growth factor beta in endothelial cells.
机构信息
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA.
出版信息
FEBS Lett. 2012 Sep 21;586(19):3317-23. doi: 10.1016/j.febslet.2012.07.008. Epub 2012 Jul 20.
Abstract
Here we show that tyrosine phosphorylation of caveolin-2 (Cav-2) negatively regulates the anti-proliferative function of transforming growth factor beta (TGF-beta) in endothelial cells. In contrast to wild-type-Cav-2, retroviral re-expression of Y19/27F-Cav-2 in Cav-2 knockout endothelial cells did not affect anti-proliferative effect of TGF-beta compared to empty vector. Conversely, although less effective than wild-type, re-expression of S23/36A-Cav-2 reduced the effect of TGF-beta compared to empty vector. This differential effect of tyrosine and serine phosphorylation mutants of Cav-2 correlated with TGF-beta-induced Smad3 phosphorylation and transcriptional activation of plasminogen activator inhibitor-1. Thus tyrosine-phosphorylated Cav-2 counteracts anti-proliferative effect of TGF-beta in endothelial cells.
摘要
在这里，我们表明 Cav-2（小窝蛋白-2）的酪氨酸磷酸化负调控转化生长因子β（TGF-β）在血管内皮细胞中的抗增殖功能。与野生型 Cav-2 相反，与空载体相比，在 Cav-2 敲除的内皮细胞中，通过逆转录病毒重新表达 Y19/27F-Cav-2 并不影响 TGF-β的抗增殖作用。相反，尽管比野生型 Cav-2 效果差，但是 S23/36A-Cav-2 的重新表达与空载体相比降低了 TGF-β的作用。Cav-2 的酪氨酸和丝氨酸磷酸化突变体的这种差异作用与 TGF-β诱导的 Smad3 磷酸化和纤溶酶原激活物抑制剂-1 的转录激活相关。因此，酪氨酸磷酸化的 Cav-2 拮抗 TGF-β在血管内皮细胞中的抗增殖作用。
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