N-terminal tyrosine phosphorylation of caveolin-2 negates anti-proliferative effect of transforming growth factor beta in endothelial cells

被引:9
作者
Abel, Britain [1 ]
Willoughby, Cara [1 ]
Jang, Sungchan [1 ]
Cooper, Laura [1 ]
Xie, Leike [1 ]
Vo-Ransdell, Chi [1 ]
Sowa, Grzegorz [1 ]
机构
[1] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65212 USA
关键词
Caveolin-2; N-terminal tyrosine and serine phosphorylation; TGF-beta; Smad3; PAI-1; Endothelial cell proliferation; GENE FAMILY; PROTEIN; EXPRESSION; SERINE-23; COMPONENT; SEQUENCE; MUSCLE;
D O I
10.1016/j.febslet.2012.07.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:3317 / 3323
页数:7
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