Src tyrosine kinase regulates angiotensin II-induced protein kinase Cζ activation and proliferation in vascular smooth muscle cells

Protein kinase C zeta (PKC zeta) isoform plays a critical role in angiotensin II (AngII)-elicited extracellular signal-regulated kinase 1/2 (ERK1/2) activation and proliferation in vascular smooth muscle cells (VSMCs). However, the exact signal transduction mechanism by which AngII activates PKC zeta has not been clarified. In this study, we investigated the role of Src in PKC zeta activation and VSMCs proliferation induced by AngII. AngII-induced rapid activation of PKC zeta, which was associated with its phosphorylation and nuclear translocation. AngII not only induced Src activation but also promoted the physical association between Src and PKC zeta, which was abolished by Src inhibition with PP2. Src inhibition also abrogated AngII-stimulated PKC zeta activation, ERK1/2 phosphorylation and VSMCs proliferation. In conclusion, Src kinase plays an important role in AngII-elicited PKC zeta activation and the subsequent downstream signaling including ERK1/2 activation and VSMCs proliferation. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.