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

Protein kinase Czeta (PKCzeta) 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 PKCzeta has not been clarified. In this study, we investigated the role of Src in PKCzeta activation and VSMCs proliferation induced by AngII. AngII-induced rapid activation of PKCzeta, which was associated with its phosphorylation and nuclear translocation. AngII not only induced Src activation but also promoted the physical association between Src and PKCzeta, which was abolished by Src inhibition with PP2. Src inhibition also abrogated AngII-stimulated PKCzeta activation, ERK1/2 phosphorylation and VSMCs proliferation. In conclusion, Src kinase plays an important role in AngII-elicited PKCzeta activation and the subsequent downstream signaling including ERK1/2 activation and VSMCs proliferation. Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.