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

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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.
Funding Information
  • National Institute of Health (1R01HL081860)

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