c-Src Induces Phosphorylation and Translocation of p47phox

Abstract

Objectives— The aim of this study was to determine molecular mechanisms whereby c-Src regulates angiotensin II (Ang II)-mediated NAD(P)H oxidase-derived ·O₂⁻ in human vascular smooth muscle cells (VSMCs). Methods and Results— VSMCs from human small arteries were studied. Ang II increased NAD(P)H oxidase-mediated generation of ·O₂⁻ and H₂O₂ (P−/− mice. Ang II-induced ·O₂⁻ generation was lower in c-Src^−/− than c-Src^+/+ counterparts. This was associated with decreased p47phox phosphorylation, blunted Ang II-stimulated NAD(P)H oxidase activation, and failure of Ang II to increase subunit expression. Conclusions— c-Src regulates NAD(P)H oxidase-derived ·O₂⁻ generation acutely by stimulating p47phox phosphorylation and translocation and chronically by increasing protein content of gp91phox, p22phox, and p47phox in Ang II-stimulated cells. These novel findings identify NAD(P)H oxidase subunits, particularly p47phox, as downstream targets of c-Src.