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

J. Biol. Chem., Vol. 281, Issue 23, 16043-16051, June 9, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/23/16043    most recent M601823200v1 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 Liu, Z. Articles by Whitehead, I. P. Search for Related Content PubMed PubMed Citation Articles by Liu, Z. Articles by Whitehead, I. P. Social Bookmarking                      What's this?

Transformation by the Rho-specific Guanine Nucleotide Exchange Factor Dbs Requires ROCK I-mediated Phosphorylation of Myosin Light Chain^*

From the Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103

Dbs was identified in a cDNA-based expression screen for sequences that can cause malignant growth when expressed in murine fibroblasts. In previous studies we have shown that Dbs is a Rho-specific guanine nucleotide exchange factor that can activate RhoA and/or Cdc42 in a cell-specific manner. In this current study we have used a combination of genetic and pharmacological approaches to examine the relative contributions of RhoA·PRK and RhoA·ROCK signaling to Dbs transformation. Our analysis indicates that ROCK is activated in Dbs-transformed cells and that Dbs transformation is dependent upon ROCK I activity. In contrast, there appears to be no requirement for PRK activation in Dbs transformation. Dbs transformation is also associated with increased phosphorylation of myosin light chain and stress fiber formation, both of which occur in a ROCK-dependent manner. Suppression of myosin light chain expression by small interfering RNAs impairs Dbs focus formation, thus establishing a direct link between actinomyosin contraction and Rho-specific guanine nucleotide exchange factor transformation.

Received for publication, February 24, 2006 , and in revised form, April 11, 2006.

^* This work was supported by NCI, National Institutes of Health Public Health Services Grant CA97066 and American Cancer Society Research Scholar Grant RGS-04-199-01 (to I. P. W.). 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 Recipient of Ruth Kirchstein Postdoctoral Fellowship CA113049 [GenBank] .

² Recipient of Ruth Kirchstein Predoctoral Fellowship CA117049 [GenBank] .

³ To whom correspondence should be addressed: Dept. of Microbiology and Molecular Genetics, International Center for Public Health, 225 Warren St., Newark, NJ 07103. Tel.: 973-972-4483 (ext. 25215); Fax: 973-972-3644; E-mail: whiteip{at}umdnj.edu.

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

This article has been cited by other articles:

				E. V. Kostenko, O. O. Olabisi, S. Sahay, P. L. Rodriguez, and I. P. Whitehead Ccpg1, a Novel Scaffold Protein That Regulates the Activity of the Rho Guanine Nucleotide Exchange Factor Dbs Mol. Cell. Biol., December 1, 2006; 26(23): 8964 - 8975. [Abstract] [Full Text] [PDF]