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Src and Cas Are Essentially but Differentially Involved in Angiotensin II-stimulated Migration of Vascular Smooth Muscle Cells via Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH2-terminal Kinase Activation

Src and Cas Are Essentially but Differentially Involved in Angiotensin II-stimulated Migration of Vascular Smooth Muscle Cells via Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH2-terminal Kinase Activation

Moe Kyaw, Masanori Yoshizumi, Koichiro Tsuchiya, Shoji Kagami, Yuki Izawa, Yoshiko Fujita, Nermin Ali, Yasuhisa Kanematsu, Kazunori Toida, Kazunori Ishimura, Toshiaki Tamaki

Mol Pharmacol. 2004 Apr;65(4):832-41.

PMID: 15044612

Abstract:

Angiotensin II (Ang II) plays an important role in several cardiovascular diseases associated with vascular smooth muscle cell (VSMC) growth and migration. Src activity is known to be required for the migration of a number of cell types. p130Cas was reported to be essential for cell migration and actin filament reorganization. Mitogen-activated protein (MAP) kinases were also reported to be critical regulatory factors for growth and migration of VSMC. However, precise intracellular mechanisms involving c-Src, p130Cas, and MAP kinases in Ang II-stimulated migration of VSMC have not been well elucidated. Here we demonstrated that Ang II rapidly and significantly stimulated tyrosine phosphorylation of Src and Cas and their association in rat aortic smooth muscle cells (RASMC). Ang II-stimulated tyrosine phosphorylation of Src and Cas and activation of ERK1/2 and JNK, but not p38, were potently inhibited by Src family tyrosine kinase inhibitors, herbimycin A (HA) and PP2. Ang II-stimulated Src and Cas association, tyrosine phosphorylation of Cas, and activation of ERK1/2 and JNK were suppressed in kinase-inactive Src (KI Src)-overexpressed RASMC. Ang II-stimulated JNK activation but not ERK1/2 activation was blocked in substrate domain-deleted Cas (DeltaSD Cas)-overexpressed RASMC. In addition, HA, PP2, ERK1/2 inhibitor, 2'-amino-3'-methoxyflavone (PD98059) and JNK inhibitor, and anthra[1,9-cd]pyrazol-6(2H)-one (SP600125) significantly inhibited Ang II-stimulated migration of RASMC. Ang II-induced colocalization of Src and Cas and migration were inhibited in both KI Src- and DeltaSD Cas-overexpressed RASMC. These findings suggest that Src and Cas are essentially but differentially involved in Ang II-stimulated migration of VSMC through the activation of ERK1/2 and JNK.

Chemicals Related in the Paper:

Catalog Number	Product Name	CAS Number	Price
AP129566	JNK Inhibitor II - CAS 129-56-6	129-56-6	Price
AP172889279	PP2 - CAS 172889-27-9	172889-27-9	Price
AP219138246	p38 MAP Kinase Inhibitor - CAS 219138-24-6	219138-24-6	Price
AP459848352	Src Kinase Inhibitor II - CAS 459848-35-2	459848-35-2	Price

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