c-Src-mediated phosphorylation of TRIP6 regulates its function in lysophosphatidic acid-induced cell migration

Yun-Ju Lai, Chen Shan Chen, Weei Chin Lin, Fang Tsyr Lin

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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 TRJP6 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.

Original languageEnglish
Pages (from-to)5859-5868
Number of pages10
JournalMolecular and Cellular Biology
Volume25
Issue number14
DOIs
Publication statusPublished - 2005 Jul 1

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Receptor-Interacting Protein Serine-Threonine Kinases
Cell Movement
Thyroid Gland
Phosphorylation
Zyxin
Fibroblasts
Lysophosphatidic Acid Receptors
lysophosphatidic acid
NIH 3T3 Cells
Phosphotyrosine
Focal Adhesions
Aptitude
Proline
Tyrosine
Actins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

c-Src-mediated phosphorylation of TRIP6 regulates its function in lysophosphatidic acid-induced cell migration. / Lai, Yun-Ju; Chen, Chen Shan; Lin, Weei Chin; Lin, Fang Tsyr.

In: Molecular and Cellular Biology, Vol. 25, No. 14, 01.07.2005, p. 5859-5868.

Research output: Contribution to journalArticle

Lai, Yun-Ju ; Chen, Chen Shan ; Lin, Weei Chin ; Lin, Fang Tsyr. / c-Src-mediated phosphorylation of TRIP6 regulates its function in lysophosphatidic acid-induced cell migration. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 14. pp. 5859-5868.
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