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

J. Biol. Chem., Vol. 282, Issue 33, 24381-24387, August 17, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/33/24381    most recent M701499200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lai, Y.-J. Articles by Lin, F.-T. Search for Related Content PubMed PubMed Citation Articles by Lai, Y.-J. Articles by Lin, F.-T. Social Bookmarking                      What's this?

PTPL1/FAP-1 Negatively Regulates TRIP6 Function in Lysophosphatidic Acid-induced Cell Migration^*

Yun-Ju Lai¹, Weei-Chin Lin, and Fang-Tsyr Lin²

From the Department of Cell Biology and Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005

The LIM domain-containing TRIP6 (Thyroid Hormone Receptor-interacting Protein 6) is a focal adhesion molecule known to regulate lysophosphatidic acid (LPA)-induced cell migration through interaction with the LPA₂ receptor. LPA stimulation targets TRIP6 to the focal adhesion complexes and promotes c-Src-dependent phosphorylation of TRIP6 at Tyr-55, which creates a docking site for the Crk Src homology 2 domain, thereby promoting LPA-induced morphological changes and cell migration. Here we further demonstrate that a switch from c-Src-mediated phosphorylation to PTPL1/Fas-associated phosphatase-1-dependent dephosphorylation serves as an inhibitory feedback control mechanism of TRIP6 function in LPA-induced cell migration. PTPL1 dephosphorylates phosphotyrosine 55 of TRIP6 in vitro and inhibits LPA-induced tyrosine phosphorylation of TRIP6 in cells. This negative regulation requires a direct protein-protein interaction between these two molecules and the phosphatase activity of PTPL1. In contrast to c-Src, PTPL1 prevents TRIP6 turnover at the sites of adhesions. As a result, LPA-induced association of TRIP6 with Crk and the function of TRIP6 to promote LPA-induced morphological changes and cell migration are inhibited by PTPL1. Together, these results reveal a novel mechanism by which PTPL1 phosphatase plays a counteracting role in regulating TRIP6 function in LPA-induced cell migration.

Received for publication, February 20, 2007 , and in revised form, June 25, 2007.

^* This work was supported in part by National Institutes of Health Grant CA100848 (to F.-T. L.). 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1 and supplemental videos S1-S4.

¹ Recipient of an American Heart Association predoctoral fellowship.

² To whom correspondence should be addressed: Dept. of Cell Biology, The University of Alabama at Birmingham, MCLM 360A, 1918 University Blvd., Birmingham, AL 35294-0005. Tel.: 205-975-5060; Fax: 205-975-5648; E-mail: flin{at}uab.edu.

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

This article has been cited by other articles:

				J. L. Crowley, T. C. Smith, Z. Fang, N. Takizawa, and E. J. Luna Supervillin Reorganizes the Actin Cytoskeleton and Increases Invadopodial Efficiency Mol. Biol. Cell, February 1, 2009; 20(3): 948 - 962. [Abstract] [Full Text] [PDF]