AJP - Heart Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (October 7, 2004). doi:10.1152/ajpheart.00519.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/2/H936    most recent
00519.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Radel, C.
Right arrow Articles by Rizzo, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Radel, C.
Right arrow Articles by Rizzo, V.
Submitted on May 28, 2004
Accepted on September 12, 2004

Integrin Mechanotransduction Stimulates Caveolin-1 Phosphorylation and Recruitment of Csk to Mediate Actin Reorganization

C. Radel1 and V. Rizzo1*

1 Center for Cardiovascular Sciences, Albany Medical College, Albany, NY, USA

* To whom correspondence should be addressed. E-mail: rizzov{at}temple.edu.

To identify the role of caveolin-1 in integrin mechanotransduction, we exposed BAEC to 10 dynes/cm2 of laminar shear stress. Caveolin-1 was acutely and transiently phosphorylated with shear, occurring downstream of {beta}1 integrin activation as the {beta}1 integrin blocking antibody, JB1A, was inhibitory. In manipulating Src-family kinase (SFK) activity with knockdown of Csk or 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 {beta}1 integrin sites in a {beta}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 {beta}1 integrin sites. Like caveolin-1, treatment with JB1A and PP1 attenuated shear-induced Csk association with {beta}1 integrins. Csk function was assayed with transfection of a caveolin-1 phosphorylation-domain peptide. The peptide attenuated shear-induced association of Csk at {beta}1 integrin sites, as well as, co-localization of Csk with paxillin and phosphorylated caveolin-1. Since 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 di-phosphorylation due to shear. Disruption of Csk/integrin association by peptide treatment was also inhibitory of the MLC di-phosphorylation response. Together these data indicate integrin activation with shear stress results in SFK regulated caveolin-1 phosphorylation which, in turn, mediates Csk association at integrin sites where it plays a role in downstream, shear-stimulated MLC di-phosphorylation.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
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]

Home page
 J. Biol. Chem.Home page
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]

Home page
 Am. J. Physiol. Renal Physiol.Home page
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]

Home page
 J. Physiol.Home page
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]

Home page
 J. Cell Sci.Home page
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]

Home page
 JCBHome page
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]

Home page
 J. Am. Soc. Nephrol.Home page
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]

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

Home page
 Cancer Res.Home page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.