Regulation of phospholipase C-β3 activity by Na+/H+ exchanger regulatory factor 2

Jong Ik Hwang, Kyun Heo, Kum Joo Shin, Eunjoon Kim, C. H.Chris Yun, Sung Ho Ryu, Hee Sup Shin, Pann Ghill Suh

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85 Citations (Scopus)


Among the phospholipase C that catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate, four mammalian phospholipase C-β (PLC-β) isotypes (isotypes 1-4) are activated through G protein-coupled receptors (GPCRs). Although the regulation of the PLC-βs by GPCRs and heterotrimeric G proteins has been extensively studied, little is known about the molecular determinants that regulate their activity. The PLC-β isozymes carry a putative PSD-95/Dlg/ZO-1 (PDZ) binding motif (X(S/T)X(V/L)COOH) at their carboxyl terminus, which is implicated in specific interactions with anchor proteins. Using the yeast two-hybrid system, we identified Na+/H+ exchanger regulatory factor 2 (NHERF2) as a protein that interacted with a C- terminal heptapeptide of PLC-β3. Immunoprecipitation studies revealed that NHERF2 interacts specifically with PLCβ3, but not with other PLC-β isotypes. Furthermore, PLC-β3 interacted with NHERF2 rather than with other PDZ-containing proteins. This interaction required the COOH-terminal NTQL sequence of PLC-β3 and the second PDZ domain of NHERF2. Interestingly, NHERF2 potentiated the PLC-β activation by carbachol in COS7 and HeLa cells, while mutant NHERF2, lacking the second PDZ domain, had no such effect. Taken together, the data suggest that NHERF2 may act as a modulator underlying the process of PLC-β3-mediated signaling.

Original languageEnglish
Pages (from-to)16632-16637
Number of pages6
JournalJournal of Biological Chemistry
Issue number22
Publication statusPublished - 2000 Jun 2
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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