Format

Send to

Choose Destination
See comment in PubMed Commons below
J Clin Invest. 1999 Mar;103(6):789-97.

Agonist-stimulated cytoskeletal reorganization and signal transduction at focal adhesions in vascular smooth muscle cells require c-Src.

Author information

1
Department of Medicine, Cardiology Division, University of Washington School of Medicine, Seattle, Washington 98195, USA. tishida@mcai.med.hiroshima-u.ac.jp

Abstract

Thrombin and angiotensin II (angII) have trophic properties as mediators of vascular remodeling. Focal adhesions and actin cytoskeleton are involved in cell growth, shape, and movement and may be important in vascular remodeling. To characterize mechanisms by which thrombin and angII modulate vessel structure, we studied the effects of these G protein-coupled receptor ligands on focal adhesions in vascular smooth muscle cells (VSMCs). Both thrombin and angII stimulated bundling of actin filaments to form stress fibers, assembly of focal adhesions, and protein tyrosine phosphorylation at focal adhesions, such as p130Cas, paxillin, and tensin. To test whether c-Src plays a critical role in focal adhesion rearrangement, we analyzed cells with altered c-Src activity by retroviral transduction of wild-type (WT) and kinase-inactive (KI) c-Src into rat VSMCs, and by use of VSMCs from WT (src+/+) and Src-deficient (src-/-) mice. Tyrosine phosphorylation of Cas, paxillin, and tensin were markedly decreased in VSMCs expressing KI-Src and in src-/- VSMCs. Expression of KI-Src did not inhibit stress fiber formation by thrombin. Surprisingly, actin bundling was markedly decreased in VSMCs from src-/- mice both basally and after thrombin stimulation, compared with src+/+ mice. We also studied the effect of KI-Src and WT-Src on VSMC spreading. Expression of KI-Src reduced the rate of VSMC spreading on collagen, whereas WT-Src enhanced cell spreading. In conclusion, c-Src plays a critical role in agonist-stimulated cytoskeletal reorganization and signal transduction at focal adhesions in VSMCs. c-Src kinase activity is required for the cytoskeletal turnover that occurs in cell spreading, whereas c-Src appears to regulate actin bundling via a kinase-independent mechanism.

PMID:
10079099
PMCID:
PMC408136
DOI:
10.1172/JCI4189
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Society for Clinical Investigation Icon for PubMed Central
    Loading ...
    Support Center