Lysophosphatidic acid 2 receptor-mediated supramolecular complex formation regulates its antiapoptotic effect.
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.
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