Caveolin-1 is transiently dephosphorylated by shear stress-activated protein tyrosine phosphatase mu

Endothelial cells are subjected to hemodynamic shear stress, which regulates multiple vascular functions partially by the caveolin-1-dependent mechanisms. Caveolin-1 is a principal protein in the plasma membrane microdomains called caveolae and interacts with various signaling molecules. Recently, caveolin-1 was elucidated to be phosphorylated on tyrosine 14. However, it is not known how phosphorylation of caveolin-1 is controlled in endothelium. In this study, we found that caveolin-1 is phosphorylated by p38 mitogen-activated protein kinase (MAPK) under a static condition. When endothelial cells were exposed to shear stress, caveolin-1 was transiently dephosphorylated. Since the activity of p38 MAPK was not affected by shear stress, the shear-dependent dephosphorylation of caveolin-1 was not mediated by p38 MAPK. Of interest, sodium orthovanadate, an inhibitor for phosphatases, blocked the shear-dependent dephosphorylation of caveolin-1. We also observed that protein tyrosine phosphatase mu was transiently activated by shear stress, suggesting its role in the dephosphorylation of caveolin-1.