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Lysophosphatidic acid 2 receptor-mediated supramolecular complex formation regulates its antiapoptotic effect.
E, Shuyu; Lai, Yun-Ju; Tsukahara, Ryoko; Chen, Chen-Shan; Fujiwara, Yuko; Yue, Junming; Yu, Jei-Hwa; Guo, Huazhang; Kihara, Akio; Tigyi, Gábor; Lin, Fang-Tsyr.
Affiliation
  • E S; Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
J Biol Chem ; 284(21): 14558-71, 2009 May 22.
Article in En | MEDLINE | ID: mdl-19293149
The G protein-coupled lysophosphatidic acid 2 (LPA(2)) receptor elicits prosurvival responses to prevent and rescue cells from apoptosis. However, G protein-coupled signals are not sufficient for the full protective effect of LPA(2). LPA(2) differs from other LPA receptor subtypes in the C-terminal tail, where it contains a zinc finger-binding motif for the interactions with LIM domain-containing TRIP6 and proapoptotic Siva-1, and a PDZ-binding motif through which it complexes with the NHERF2 scaffold protein. In this report, we identify a unique CXXC motif of LPA(2) responsible for the binding to TRIP6 and Siva-1, and demonstrate that disruption of these macromolecular complexes or knockdown of TRIP6 or NHERF2 expression attenuates LPA(2)-mediated protection from chemotherapeutic agent-induced apoptosis. In contrast, knockdown of Siva-1 expression enhances this effect. Furthermore, a PDZ-mediated direct interaction between TRIP6 and NHERF2 facilitates their interaction with LPA(2). Together, these results suggest that in addition to G protein-activated signals, the cooperation embedded in the LPA(2)-TRIP6-NHERF2 ternary complex provides a novel ligand-dependent signal amplification mechanism that is required for LPA(2)-mediated full activation of antiapoptotic signaling.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Apoptosis / Receptors, Lysophosphatidic Acid Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: J Biol Chem Year: 2009 Document type: Article Affiliation country: United States Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Apoptosis / Receptors, Lysophosphatidic Acid Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: J Biol Chem Year: 2009 Document type: Article Affiliation country: United States Country of publication: United States