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Src modulates contractile vascular smooth muscle function via regulation of focal adhesions
Author(s) -
Min Jianghong,
Reznichenko Maya,
Poythress Ransom H.,
Gallant Cynthia M.,
Vetterkind Susanne,
Li Yunping,
Morgan Kathleen G.
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24062
Subject(s) - focal adhesion , paxillin , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , contractility , phosphorylation , vascular smooth muscle , biology , chemistry , endocrinology , smooth muscle
Abstract Src is a known regulator of focal adhesion turnover in migrating cells; but, in contrast, Src is generally assumed to play little role in differentiated, contractile vascular smooth muscle (dVSM). The goal of the present study was to determine if Src‐family kinases regulate focal adhesion proteins and how this might affect contractility of non‐proliferative vascular smooth muscle. We demonstrate here, through the use of phosphotyrosine screening, deconvolution microscopy imaging, and differential centrifugation, that the activity of Src family kinases in aorta is regulated by the alpha agonist and vasoconstrictor phenylephrine, and leads to focal adhesion protein phosphorylation and remodeling in dVSM. Furthermore, Src inhibition via morpholino knockdown of Src or by the small molecule inhibitor PP2 prevents phenylephrine‐induced adhesion protein phosphorylation, markedly slows the tissue's ability to contract, and decreases steady state contractile force amplitude. Significant vasoconstrictor‐induced and Src‐dependent phosphorylation of Cas pY‐165, FAK pY‐925, paxillin pY‐118, and Erk1/2 were observed. However, increases in FAK 397 phosphorylation were not seen, demonstrating differences between cells in tissue versus migrating, proliferating cells. We show here that Src, in a cause and effect manner, regulates focal adhesion protein function and, consequently, modulates contractility during the action of a vasoconstrictor. These data point to the possibility that vascular focal adhesion proteins may be useful drug discovery targets for novel therapeutic approaches to cardiovascular disease. J. Cell. Physiol. 227: 3585–3592, 2012. © 2012 Wiley Periodicals, Inc.