HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/2/H936    most recent 00519.2004v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (36) Citing Articles via Google Scholar Google Scholar Articles by Radel, C. Articles by Rizzo, V. Search for Related Content PubMed PubMed Citation Articles by Radel, C. Articles by Rizzo, V.

Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization

Center for Cardiovascular Science, Albany Medical College, Albany, New York

Submitted 20 August 2004 ; accepted in final form 22 September 2004

To identify the role of caveolin-1 in integrin mechanotransduction, we exposed bovine aortic endothelial cells to 10 dyn/cm² of laminar shear stress. Caveolin-1 was acutely and transiently phosphorylated with shear, occurring downstream of ₁-integrin activation as the ₁-integrin blocking antibody JB1A was inhibitory. In manipulating Src family kinase (SFK) activity with knockdown of Csk or type 1 protein phosphatase (PP1) treatment, we observed coordinate increase and decrease in shear-induced caveolin-1 phosphorylation, respectively. Hence, shear-stimulated caveolin-1 phosphorylation is regulated by SFKs. Shear-induced recruitment and phosphorylation of caveolin-1 occurred at ₁-integrin sites in a ₁-integrin- and SFK-dependent manner. Csk, described to interact with pY14-caveolin-1 and integrins, bound to an increased pool of phosphorylated caveolin-1 after shear corresponding with elevated Csk at ₁-integrin sites. Like caveolin-1, treatment with JB1A and PP1 attenuated shear-induced Csk association with ₁-integrins. Csk function was assayed with transfection of a caveolin-1 phosphorylation domain peptide. The peptide attenuated shear-induced association of Csk at ₁-integrin sites, as well as colocalization of Csk with paxillin and phosphorylated caveolin-1. Because integrin and Csk activity regulate cytoskeletal reorganization, we evaluated the role of this mechanism in shear-induced myosin light chain (MLC) phosphorylation. Knockdown of Csk expression was sufficient to reduce MLC diphosphorylation due to shear. Disruption of Csk-integrin association by peptide treatment was also inhibitory of the MLC diphosphorylation response. Together these data indicate that integrin activation with shear stress results in SFK-regulated caveolin-1 phosphorylation that, in turn, mediates Csk association at integrin sites, where it plays a role in downstream, shear-stimulated MLC diphosphorylation.

myosin light chain; caveolae; shear stress

This article has been cited by other articles:

				J.-L. Balligand, O. Feron, and C. Dessy eNOS Activation by Physical Forces: From Short-Term Regulation of Contraction to Chronic Remodeling of Cardiovascular Tissues Physiol Rev, April 1, 2009; 89(2): 481 - 534. [Abstract] [Full Text] [PDF]

				B. Joshi, S. S. Strugnell, J. G. Goetz, L. D. Kojic, M. E. Cox, O. L. Griffith, S. K. Chan, S. J. Jones, S.-P. Leung, H. Masoudi, et al. Phosphorylated Caveolin-1 Regulates Rho/ROCK-Dependent Focal Adhesion Dynamics and Tumor Cell Migration and Invasion Cancer Res., October 15, 2008; 68(20): 8210 - 8220. [Abstract] [Full Text] [PDF]

				S. C. Kirkland and H. Ying {alpha}2{beta}1 Integrin Regulates Lineage Commitment in Multipotent Human Colorectal Cancer Cells J. Biol. Chem., October 10, 2008; 283(41): 27612 - 27619. [Abstract] [Full Text] [PDF]

				F. Peng, B. Zhang, D. Wu, A. J. Ingram, B. Gao, and J. C. Krepinsky TGF{beta}-induced RhoA activation and fibronectin production in mesangial cells require caveolae Am J Physiol Renal Physiol, July 1, 2008; 295(1): F153 - F164. [Abstract] [Full Text] [PDF]

				J. G. Goetz, B. Joshi, P. Lajoie, S. S. Strugnell, T. Scudamore, L. D. Kojic, and I. R. Nabi Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine-phosphorylated caveolin-1 J. Cell Biol., March 24, 2008; 180(6): 1261 - 1275. [Abstract] [Full Text] [PDF]

				S. Belmonte and M. Morad 'Pressure-flow'-triggered intracellular Ca2+ transients in rat cardiac myocytes: possible mechanisms and role of mitochondria J. Physiol., March 1, 2008; 586(5): 1379 - 1397. [Abstract] [Full Text] [PDF]

				S. J. Nixon, A. Carter, J. Wegner, C. Ferguson, M. Floetenmeyer, J. Riches, B. Key, M. Westerfield, and R. G. Parton Caveolin-1 is required for lateral line neuromast and notochord development J. Cell Sci., July 1, 2007; 120(13): 2151 - 2161. [Abstract] [Full Text] [PDF]

				A. Grande-Garcia, A. Echarri, J. de Rooij, N. B. Alderson, C. M. Waterman-Storer, J. M. Valdivielso, and M. A. del Pozo Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases J. Cell Biol., May 21, 2007; 177(4): 683 - 694. [Abstract] [Full Text] [PDF]

				F. Peng, D. Wu, A. J. Ingram, B. Zhang, B. Gao, and J. C. Krepinsky RhoA Activation in Mesangial Cells by Mechanical Strain Depends on Caveolae and Caveolin-1 Interaction J. Am. Soc. Nephrol., January 1, 2007; 18(1): 189 - 198. [Abstract] [Full Text] [PDF]

				D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]

				D. K. Sharma, J. C. Brown, Z. Cheng, E. L. Holicky, D. L. Marks, and R. E. Pagano The Glycosphingolipid, Lactosylceramide, Regulates {beta}1-Integrin Clustering and Endocytosis Cancer Res., September 15, 2005; 65(18): 8233 - 8241. [Abstract] [Full Text] [PDF]