Src Regulates Sphingosine-1-Phosphate Mediated Smooth Muscle Cell Migration

详细信息    查看全文

• 作者：Enrico A. Duru ; Ph.D. ; Yuyang Fu ; M.D. ; Ph.D. ; Mark G. Davies ; M.D. ; Ph.D. ; M.B.A. ; ^{MDavies@tmhs.org}
• 关键词：S-1-P ; cell signaling ; cell migration ; src ; reactive oxygen species
• 刊名：Journal of Surgical Research
• 出版年：2012
• 出版时间：1 June, 2012
• 年：2012
• 卷：175
• 期：1
• 页码：30-34
• 全文大小：576 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Background

Sphingosine-1-phosphate (S-1-P) is a bioactive sphingolipid released from activated platelets at sites of arterial injury that stimulates migration of smooth muscle cells (SMC). The kinase src is a significant focal point in transmembrane signaling. This study examines the role of src during smooth muscle cell migration in response to S-1-P.

Methods

Human coronary arterial SMCs were cultured in?vitro. Boyden microchemotaxis assays of migration were performed in response to S-1-P in the presence and absence the src inhibitor (PP2, 10 ¦ÌM) and a dominant negative src construct (DNsrc). siRNA to S-1-P receptors was used to down-regulate the S-1-P receptors. Western blotting was performed for src and MAPK phosphorylation.

Results

Inhibition of src with PP2 but not PP3 partially blocked S-1-P-mediated cell migration. S-1-P induced time-dependent activation of src, which was inhibited by PP2 and adenoviral DNsrc. PP3 or an empty vector had no effect. Activation of src by S-1-P was inhibited by siRNA to S-1-PR1 and S-1-PR3 but not by S-1-PR2. When the VSMC were transfected with adenovirus containing ¦ÂARK_CT, an inhibitor to G¦Â¦Ã, src activation was significantly attenuated. Src inhibition with PP2 reduced p38^MAPK and JNK activation but did not alter ERK1/2 activation.

Conclusion

S-1-P mediated VSMC migration is modulated by a G-protein-coupled src pathway partially through src-mediated p38^MAPK and JNK signaling and requires S-1-PR1 and S-1-PR3 receptors.