TRIP6 Enhances Lysophosphatidic Acid-induced Cell Migration by Interacting with the Lysophosphatidic Acid 2 Receptor

Jun Xu, Yun Ju Lai, Weei Chin Lin, Fang Tsyr Lin

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Lysophosphatidic acid (LPA) induces actin rearrangement, focal adhesion assembly, and cell migration through the activation of small G protein Rho and its downstream effectors. These diverse cellular responses are mediated by its associated G protein-coupled receptors. However, the mechanisms and specificity by which these LPA receptors mediate LPA actions are still poorly understood. Here we show that LPA stimulation promotes the interaction of the LPA 2 receptor with a focal adhesion molecule, TRIP6 (thyroid receptor interacting protein 6)/ZRP-1 (zyxin-related protein 1). TRIP6 directly binds to the carboxyl-terminal tail of the LPA2 receptor through its LIM domains. LPA-dependent recruitment of TRIP6 to the plasma membrane promotes its targeting to focal adhesions and co-localization with actin stress fibers. In addition, TRIP6 associates with the components of focal complexes including paxillin, focal adhesion kinase, c-Src, and p130cas in an agonist-dependent manner. Overexpression of TRIP6 augments LPA-induced cell migration; in contrast, suppression of endogenous TRIP6 expression by a TRIP6-specific small interfering RNA reduces it in SKOV3 ovarian cancer cells. Strikingly, the association with TRIP6 is specific to the LPA2 receptor but not LPA1 or LPA3 receptor, indicating a specific role for TRIP6 in regulating LPA2 receptor-mediated signaling. Taken together, our results suggest that TRIP6 functions at a point of convergence between the activated LPA2 receptor and downstream signals involved in cell adhesion and migration.

Original languageEnglish
Pages (from-to)10459-10468
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number11
DOIs
Publication statusPublished - 2004 Mar 12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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