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Agonist-stimulated cytoskeletal reorganization and signal transduction at focal adhesions in vascular smooth muscle cells require c-Src
Takafumi Ishida, … , Masafumi Takahashi, Bradford C. Berk
Takafumi Ishida, … , Masafumi Takahashi, Bradford C. Berk
Published March 15, 1999
Citation Information: J Clin Invest. 1999;103(6):789-797. https://doi.org/10.1172/JCI4189.
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Article

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

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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.

Authors

Takafumi Ishida, Mari Ishida, James Suero, Masafumi Takahashi, Bradford C. Berk

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Figure 8

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The effect of retroviral and adenoviral expression of kinase-inactive (K...
The effect of retroviral and adenoviral expression of kinase-inactive (KI) c-Src on thrombin-induced stress fibers in VSMCs. Serum-starved VSMC were infected with retroviral vector alone (a and b) or with retrovirus encoding KI-Src (c and d). Cells were then stimulated with 3 U/ml thrombin for 20 min. Cells were fixed and stained with FITC-phalloidin for actin. There was no effect of KI-src on thrombin-mediated actin bundling (b vs. d). VSMCs were infected with AdLazZ (e and g) or AdKI-Src (f and h). After 24-h serum starvation, cells were stimulated with 3 U/ml thrombin for 20 min, fixed, and stained with FITC-phalloidin for actin (e and f). The same cells were also stained with anti–avian Src (g and h). Note that expression of KI-Src varies in individual cells (h), without change in actin staining (f). Again, KI-Src did not alter thrombin-mediated actin bundling.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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