Lysophosphatidic acid (LPA) activates a family of cognate G protein-coupled receptors and is involved in various pathophysiological processes. However, it is not clearly understood how these LPA receptors are specifically coupled to their downstream signaling molecules. This study found that LPA2, but not the other LPA receptor isoforms, specifically interacts with Na+/H+ exchanger regulatory factor2 (NHERF2). In addition, the interaction between them requires the C-terminal PDZ domain-binding motif of LPA2 and the second PDZ domain of NHERF2. Moreover, the stable expression of NHERF2 potentiated LPA-induced phospholipase C-β (PLC-β) activation, which was markedly attenuated by either a mutation in the PDZ-binding motif of LPA2 or by the gene silencing of NHERF2. Using its second PDZ domain, NHERF2 was found to indirectly link LPA2 to PLC-β3 to form a complex, and the other PLC-β3 isozymes were not included in the protein complex. Consistently, LPA 2-mediated PLC-β activation was specifically inhibited by the gene silencing of PLC-β3. In addition, NHERF2 increases LPA-induced ERK activation, which is followed by cyclooxygenase-2 induction via a PLC-dependent pathway. Overall, the results suggest that a ternary complex composed of LPA2, NHERF2, and PLC-β3 may play a key role in the LPA 2-mediated PLC-β signaling pathway.
|Number of pages||11|
|Journal||Molecular and cellular biology|
|Publication status||Published - 2004 Jun|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology