This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Iwasaki, H. Articles by Hirata, Y. Search for Related Content PubMed PubMed Citation Articles by Iwasaki, H. Articles by Hirata, Y.

Activation of Cell Adhesion Kinase ß by Mechanical Stretch in Vascular Smooth Muscle Cells

Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan

Address all correspondence and requests for reprints to: Yukio Hirata, M.D., Ph.D., Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail: yhirata.cme{at}tmd.ac.jp.

We have studied whether activation of cell adhesion kinase ß (CAKß) is involved in stretch-induced signaling pathway in cultured rat vascular smooth muscle cells. Cyclic stretch (1 Hz) induced a rapid (within 1 min) phosphorylation of CAKß, whose effect was time and strength dependent. Both Ca²⁺ and Na⁺ ionophores (A23187 and monensin) stimulated phosphorylation of CAKß in a similar fashion to mechanical stretch. The stretch-induced phosphorylation of CAKß was inhibited completely by an intracellular Ca²⁺ chelator [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester)] and largely by gadolinium, but only partially by an extracellular Ca²⁺ chelator (EGTA). An angiotensin type 1 receptor antagonist (CV11974) abolished the phosphorylation of CAKß stimulated by angiotensin II, but not by mechanical stretch. Mechanical stretch rapidly (within 1 min) increased the association of CAKß with c-Src, but not pp125^{focal adhesion kinase}. Stretch-induced phosphorylation of ERK1/2 was inhibited by EGTA and an inhibitor of the Src kinase family [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine], but not by cytochalasin D, to disrupt actin polymerization. 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine or cytochalasin D did not affect stretch-induced phosphorylation of CAKß. These data suggest that mechanical stretch stimulates activation of CAKß, followed by its association with c-Src, which requires ion influx mainly via stretch-activated nonselective ion channels, thereby leading to activation of the p21^Ras/ERK1/2 cascade in vascular smooth muscle cells.

This article has been cited by other articles:

				Y. C. Yung, J. Chae, M. J. Buehler, C. P. Hunter, and D. J. Mooney Cyclic tensile strain triggers a sequence of autocrine and paracrine signaling to regulate angiogenic sprouting in human vascular cells PNAS, September 8, 2009; 106(36): 15279 - 15284. [Abstract] [Full Text] [PDF]

				X.-C. Ru, L.-B. Qian, Q. Gao, Y.-F. Li, I. C. Bruce, and Q. Xia Alcohol Induces Relaxation of Rat Thoracic Aorta and Mesenteric Arterial Bed Alcohol Alcohol., September 1, 2008; 43(5): 537 - 543. [Abstract] [Full Text] [PDF]

				V. Ohanian, K. Gatfield, and J. Ohanian Role of the Actin Cytoskeleton in G-Protein-Coupled Receptor Activation of PYK2 and Paxillin in Vascular Smooth Muscle Hypertension, July 1, 2005; 46(1): 93 - 99. [Abstract] [Full Text] [PDF]

				N. Boutahar, A. Guignandon, L. Vico, and M.-H. Lafage-Proust Mechanical Strain on Osteoblasts Activates Autophosphorylation of Focal Adhesion Kinase and Proline-rich Tyrosine Kinase 2 Tyrosine Sites Involved in ERK Activation J. Biol. Chem., July 16, 2004; 279(29): 30588 - 30599. [Abstract] [Full Text] [PDF]

				T. Yoshimoto, N. Fukai, R. Sato, T. Sugiyama, N. Ozawa, M. Shichiri, and Y. Hirata Antioxidant Effect of Adrenomedullin on Angiotensin II-Induced Reactive Oxygen Species Generation in Vascular Smooth Muscle Cells Endocrinology, July 1, 2004; 145(7): 3331 - 3337. [Abstract] [Full Text] [PDF]