Premium
Mechanism of angiotensin II‐induced c‐Src activation in Vascular Smooth Muscle Cells
Author(s) -
Yaghini Fariborz A,
Mugabe Be E,
Buharalioglu Cuneyt K,
Estes Anne M,
Malik Kafait U
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.911.5
Subject(s) - proto oncogene tyrosine protein kinase src , phosphorylation , angiotensin ii , vascular smooth muscle , chemistry , tyrosine phosphorylation , cytosol , kinase , bapta , tyrosine kinase , microbiology and biotechnology , extracellular , signal transduction , biochemistry , endocrinology , biology , receptor , smooth muscle , enzyme
Angiotensin II (Ang II) activates c‐Src tyrosine kinase leading to vascular smooth muscle cells (VSMC) growth. However, the mechanism of c‐Src activation by Ang II has not yet been established. This study was performed to investigate the role of calcium (Ca 2+ ) in Ang II‐induced c‐Src activation. Activation of c‐Src was measured by its phosphorylation using Western blot analysis and cytosolic Ca 2+ ([Ca 2+ ]i) by spectrofluorometry using Fura‐2. Ang II increased c‐Src phosphorylation and produced a biphasic increase in [Ca 2+ ]i, a rapid phase followed by sustained phase. Depletion of extracellular (EC) Ca 2+ or Ca 2+ chelator EGTA, inhibited Ang II‐induced c‐Src phosphorylation and the sustained but not the rapid phase of [Ca 2+ ]i. The intracellular (IC) Ca 2+ chelator, BAPTA, partially reduced c‐Src phosphorylation in the presence of EC Ca 2+ . Infection of VSMCs with dominant negative, but not partially active c‐Src adenovirus inhibited c‐Src phosphorylation and the rapid but not the sustained phase of [Ca 2+ ]i response to Ang II. These data suggest that Ang II promotes c‐Src phosphorylation by increasing influx of EC Ca 2+ . Moreover, c‐Src mediates the rapid phase of Ang II‐induced IC Ca 2+ release probably via generation of inositol trisphosphate consequent to PLC activation. However, the sustained phase of cytosolic Ca 2+ increaseby Ang II is independent of c‐Src phosphorylation (Supported by NIH grant 079109 from HLBI) .