Caveolin-1 regulates BMPRII localization and signaling in vascular smooth muscle cells |
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Authors: | Wertz Jeffrey W Bauer Philip M |
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Institution: | a Department of Surgery, University of Pittsburgh, BST 3, Room 6058, Pittsburgh, PA 15261, USA b Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA |
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Abstract: | Recent studies demonstrate the interaction of BMPRII and caveolin-1 in various cell types. In this study we test the hypothesis that caveolin-1 interacts with and regulates BMPRII-dependent signaling in vascular smooth muscle cells. We demonstrate that BMPRII localizes to caveolae and directly interacts with caveolin-1 in mouse aortic smooth muscle cells. We demonstrate that this interaction is mediated by the caveolin-1 scaffolding domain and is regulated by caveolin-1 phosphorylation. Downregulation of caveolin-1 via siRNA resulted in a loss of BMP-dependent SMAD phosphorylation and gene regulation. Further studies revealed that loss of caveolin-1 results in decreased BMPRII membrane localization and decreased association of BMPRII with the type I BMP receptor BMPRIa. Dominant negative caveolin-1 decreased BMPRII membrane localization suggesting a role for caveolin-1 in BMPRII trafficking. Taken together, our findings establish caveolin-1 as an important regulator of downstream signaling and membrane targeting of BMPRII in vascular smooth muscle cells. |
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Keywords: | Caveolin-1 Bone morphogenetic protein BMP2 BMPRII |
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