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

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