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

J. Biol. Chem., Vol. 279, Issue 11, 10397-10407, March 12, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/11/10397    most recent M313048200v1 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 Zhuang, S. Articles by Pilz, R. B. Search for Related Content PubMed PubMed Citation Articles by Zhuang, S. Articles by Pilz, R. B. Social Bookmarking                      What's this?

Vasodilator-stimulated Phosphoprotein Activation of Serum-response Element-dependent Transcription Occurs Downstream of RhoA and Is Inhibited by cGMP-dependent Protein Kinase Phosphorylation^*

Shunhui Zhuang, Giao T. Nguyen, Yongchang Chen, Tanima Gudi, Martin Eigenthaler, Thomas Jarchau, Ulrich Walter, Gerry R. Boss, and Renate B. Pilz

From the Department of Medicine and Cancer Center, University of California, San Diego, La Jolla, California 92093-0652 and the Institut fur Klinische Biochemie and Pathobiochemie, Klinikum der, Universitat Würzburg, 97080 Würzburg, Germany

Vasodilator-stimulated phosphoprotein (VASP) associates with cytoskeletal structures and promotes F-actin formation. RhoA, a member of the Ras superfamily of proteins, activates serum response element (SRE)-dependent transcription through changes in actin dynamics. We now show that the F-actin binding region of VASP is required for VASP stimulation of SRE-dependent transcription, and that VASP is downstream of RhoA in stimulating SRE-dependent transcription. The isolated carboxyl-terminal coiled-coil region of VASP mediates protein tetramerization and has been used as a dominant negative form of VASP; we found that it forms complexes with endogenous VASP in vivo and inhibits in a dose-dependent fashion serum-, RhoA-, and VASP-stimulated SRE-dependent transcription. Cyclic GMP-dependent protein kinase (G-kinase) inhibits RhoA activation of SRE-dependent transcription (Gudi, T., Chen, J. C., Casteel, D. E., Seasholtz, T. M., Boss, G. R., and Pilz, R. B. (2002) J. Biol. Chem. 277, 37382-37393). We now show that the G-kinase inhibition that occurs downstream of RhoA can be explained, at least in part, by G-kinase phosphorylation of VASP on Ser²³⁹ at the carboxyl-terminal end of the G-actin binding site, with some contribution by phosphorylation of Ser¹⁵⁷, which is proximal to the profilin binding site. A phosphorylation-deficient VASP mutant can partly prevent cGMP/G-kinase inhibition of serum- and RhoA-induced SRE-dependent transcription. These studies show that VASP, an important component of the cellular microfilament system, plays a major role in regulating SRE-dependent transcription, and that G-kinase regulates VASP activity.

Received for publication, December 1, 2003

^* This work was supported in part by United States Public Health Service Grants GM55586 (to R. B. P.) and CA89828 (to G. R. B.). 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.

To whom correspondence should be addressed. Tel.: 858-534-8805; Fax: 858-534-1421; E-mail: rpilz{at}ucsd.edu.

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

This article has been cited by other articles:

				S. L. Lindsay, S. Ramsey, M. Aitchison, T. Renne, and T. J. Evans Modulation of lamellipodial structure and dynamics by NO-dependent phosphorylation of VASP Ser239 J. Cell Sci., September 1, 2007; 120(17): 3011 - 3021. [Abstract] [Full Text] [PDF]

				C. Blume, P. M. Benz, U. Walter, J. Ha, B. E. Kemp, and T. Renne AMP-activated Protein Kinase Impairs Endothelial Actin Cytoskeleton Assembly by Phosphorylating Vasodilator-stimulated Phosphoprotein J. Biol. Chem., February 16, 2007; 282(7): 4601 - 4612. [Abstract] [Full Text] [PDF]

				K. Bundschu, U. Walter, and K. Schuh The VASP-Spred-Sprouty Domain Puzzle J. Biol. Chem., December 1, 2006; 281(48): 36477 - 36481. [Abstract] [Full Text] [PDF]

				F. Hofmann, R. Feil, T. Kleppisch, and J. Schlossmann Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion Physiol Rev, January 1, 2006; 86(1): 1 - 23. [Abstract] [Full Text] [PDF]

				K. E. Broderick, V. Singh, S. Zhuang, A. Kambo, J. C. Chen, V. S. Sharma, R. B. Pilz, and G. R. Boss Nitric Oxide Scavenging by the Cobalamin Precursor Cobinamide J. Biol. Chem., March 11, 2005; 280(10): 8678 - 8685. [Abstract] [Full Text] [PDF]

				K. Kuhnel, T. Jarchau, E. Wolf, I. Schlichting, U. Walter, A. Wittinghofer, and S. V. Strelkov The VASP tetramerization domain is a right-handed coiled coil based on a 15-residue repeat PNAS, December 7, 2004; 101(49): 17027 - 17032. [Abstract] [Full Text] [PDF]

				J. W. Copeland, S. J. Copeland, and R. Treisman Homo-oligomerization Is Essential for F-actin Assembly by the Formin Family FH2 Domain J. Biol. Chem., November 26, 2004; 279(48): 50250 - 50256. [Abstract] [Full Text] [PDF]

				L. Chen, G. Daum, K. Chitaley, S. A. Coats, D. F. Bowen-Pope, M. Eigenthaler, N. R. Thumati, U. Walter, and A. W. Clowes Vasodilator-Stimulated Phosphoprotein Regulates Proliferation and Growth Inhibition by Nitric Oxide in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1403 - 1408. [Abstract] [Full Text] [PDF]