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Molecular and Cellular Biology, July 2005, p. 5859-5868, Vol. 25, No. 14
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.14.5859-5868.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
c-Src-Mediated Phosphorylation of TRIP6 Regulates Its Function in Lysophosphatidic Acid-Induced Cell Migration
Yun-Ju Lai,1
Chen-Shan Chen,1
Weei-Chin Lin,1,2 and
Fang-Tsyr Lin1*
Department of Cell Biology,1
Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-00052
Received 13 September 2004/
Returned for modification 26 November 2004/
Accepted 11 April 2005
TRIP6 (thyroid receptor-interacting protein 6), also known as ZRP-1 (zyxin-related protein 1), is a member of the zyxin family that has been implicated in cell motility. Previously we have shown that TRIP6 binds to the LPA2 receptor and associates with several components of focal complexes in an agonist-dependent manner and, thus, enhances lysophosphatidic acid (LPA)-induced cell migration. Here we further report that the function of TRIP6 in LPA signaling is regulated by c-Src-mediated phosphorylation of TRIP6 at the Tyr-55 residue. LPA stimulation induces tyrosine phosphorylation of endogenous TRIP6 in NIH 3T3 cells and c-Src-expressing fibroblasts, which is virtually eliminated in Src-null fibroblasts. Strikingly, both phosphotyrosine-55 and proline-58 residues of TRIP6 are required for Crk binding in vitro and in cells. Mutation of Tyr-55 to Phe does not alter the ability of TRIP6 to localize at focal adhesions or associate with actin. However, it abolishes the association of TRIP6 with Crk and p130cas in cells and significantly reduces the function of TRIP6 to promote LPA-induced ERK activation. Ultimately, these signaling events control TRIP6 function in promoting LPA-induced morphological changes and cell migration.
* Corresponding author. Mailing address: MCLM 360A, 1918 University Blvd., Birmingham, AL 35294-0005. Phone: (205) 975-5060. Fax: (205) 975-5648. E-mail:
flin{at}uab.edu.
Supplemental material for this article may be found at http://mcb.asm.org/.
Molecular and Cellular Biology, July 2005, p. 5859-5868, Vol. 25, No. 14
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.14.5859-5868.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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