title: N-terminal tyrosine phosphorylation of caveolin-2 negates anti-proliferative effect of transforming growth factor beta in endothelial cells.
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.
authors: Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA.
authors: Britain
authors: B
authors: Abel
authors: Cara
authors: C
authors: Willoughby
authors: Sungchan
authors: S
authors: Jang
authors: Laura
authors: L
authors: Cooper
authors: Leike
authors: L
authors: Xie
authors: Chi
authors: C
authors: Vo-Ransdell
authors: Grzegorz
authors: G
authors: Sowa
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D051243:Caveolin 2 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055786:Gene Knockout Techniques; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D058258:Serpin E2 / Q000235:genetics; D051900:Smad3 Protein / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014443:Tyrosine / Q000737:chemistry
chemical_list: C495544:CAV2 protein, human; C495545:Cav2 protein, mouse; D051243:Caveolin 2; D050505:Mutant Proteins; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; C051321:SERPINE1 protein, human; C497790:SMAD3 protein, human; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta; D014443:Tyrosine; D012694:Serine; D017027:Protein Tyrosine Phosphatases