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

J. Biol. Chem., Vol. 281, Issue 45, 34716-34724, November 10, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/45/34716    most recent M607715200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, Q.-F. Articles by Tang, D. D. Search for Related Content PubMed PubMed Citation Articles by Li, Q.-F. Articles by Tang, D. D. Social Bookmarking                      What's this?

Critical Role of Vimentin Phosphorylation at Ser-56 by p21-activated Kinase in Vimentin Cytoskeleton Signaling^*

From the Center for Cardiovascular Sciences, Albany Medical College, Albany, New York 12208

Phosphorylation and spatial reorganization of the vimentin network have been implicated in mediating smooth muscle contraction, cell migration, and mitosis. In this study, stimulation of cultured smooth muscle cells with 5-hydroxytryptamine (5-HT) induced PAK1 phosphorylation at Thr-423 (an indication of p21-activated kinase (PAK) activation). Treatment with PAK led to disassembly of wild-type (but not mutant S56A) vimentin filaments as assessed by an in vitro filament assembly assay. Furthermore, stimulation with 5-HT resulted in the dissociation of Crk-associated substrate (CAS; an adapter protein associated with smooth muscle force development) from cytoskeletal vimentin. Expression of mutant S56A vimentin in cells inhibited the increase in phosphorylation at Ser-56 and in the ratios of soluble to insoluble vimentin (an index of vimentin disassembly) and the dissociation of CAS from cytoskeletal vimentin in response to 5-HT activation compared with cells expressing wild-type vimentin. Because CAS may be involved in PAK activation, PAK phosphorylation was evaluated in cells expressing the S56A mutant. Expression of mutant S56A vimentin depressed PAK phosphorylation at Thr-423 induced by 5-HT. Expression of the S56A mutant also inhibited the spatial reorientation of vimentin filaments in cells in response to 5-HT stimulation. Our results suggest that vimentin phosphorylation at Ser-56 may inversely regulate PAK activation possibly via the increase in the amount of soluble CAS upon agonist stimulation of smooth muscle cells. Additionally, vimentin phosphorylation at this position is critical for vimentin filament spatial rearrangement elicited by agonists.

Received for publication, August 11, 2006 , and in revised form, August 29, 2006.

^* This work was supported by NHLBI Grant HL-75388 from the National Institutes of Health and by an American Heart Association scientist development grant (to D. D. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Center for Cardiovascular Sciences, Albany Medical College, 47 New Scotland Ave., MC-8, Albany, NY 12208. Tel.: 518-262-6416; Fax: 518-262-8101; E-mail: tangd{at}mail.amc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. D. Tang and Y. Anfinogenova Physiologic Properties and Regulation of the Actin Cytoskeleton in Vascular Smooth Muscle Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2008; 13(2): 130 - 140. [Abstract] [PDF]

				D. D. Tang Intermediate filaments in smooth muscle Am J Physiol Cell Physiol, April 1, 2008; 294(4): C869 - C878. [Abstract] [Full Text] [PDF]

				W. T. Gerthoffer Migration of Airway Smooth Muscle Cells Proceedings of the ATS, January 1, 2008; 5(1): 97 - 105. [Abstract] [Full Text] [PDF]

				Y. Anfinogenova, R. Wang, Q.-f. Li, A. M. Spinelli, and D. D. Tang Abl Silencing Inhibits CAS-Mediated Process and Constriction in Resistance Arteries Circ. Res., August 17, 2007; 101(4): 420 - 428. [Abstract] [Full Text] [PDF]

				Z. Wang, A. Pandey, and G. W. Hart Dynamic Interplay between O-Linked N-Acetylglucosaminylation and Glycogen Synthase Kinase-3-dependent Phosphorylation Mol. Cell. Proteomics, August 1, 2007; 6(8): 1365 - 1379. [Abstract] [Full Text] [PDF]

				W. T. Gerthoffer Mechanisms of Vascular Smooth Muscle Cell Migration Circ. Res., March 16, 2007; 100(5): 607 - 621. [Abstract] [Full Text] [PDF]