NHERF2 specifically interacts with LPA2 receptor and defines the specificity and efficiency of receptor-mediated phospholipase C-β3 activation

Yong Seok Oh, Nam Won Jo, Jung Woong Choi, Hyeon Soo Kim, Sang Won Seo, Kyung Ok Kang, Jong Ik Hwang, Kyun Heo, Sun Hee Kim, Yun Hee Kim, In Hoo Kim, Jae Ho Kim, Yoshiko Banno, Sung Ho Ryu, Pann Ghill Suh

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Abstract

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.

Original languageEnglish
Pages (from-to)5069-5079
Number of pages11
JournalMolecular and cellular biology
Volume24
Issue number11
DOIs
Publication statusPublished - 2004 Jun

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Oh, Y. S., Jo, N. W., Choi, J. W., Kim, H. S., Seo, S. W., Kang, K. O., Hwang, J. I., Heo, K., Kim, S. H., Kim, Y. H., Kim, I. H., Kim, J. H., Banno, Y., Ryu, S. H., & Suh, P. G. (2004). NHERF2 specifically interacts with LPA2 receptor and defines the specificity and efficiency of receptor-mediated phospholipase C-β3 activation. Molecular and cellular biology, 24(11), 5069-5079. https://doi.org/10.1128/MCB.24.11.5069-5079.2004