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

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

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
Volume275
Issue number22
DOIs
Publication statusPublished - 2000 Jun 2
Externally publishedYes

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Type C Phospholipases
G-Protein-Coupled Receptors
sodium-hydrogen exchanger regulatory factor
Heterotrimeric GTP-Binding Proteins
Two-Hybrid System Techniques
Proteins
Carbachol
Phosphatidylinositols
Anchors
Hybrid systems
HeLa Cells
Immunoprecipitation
Yeast
Modulators
Isoenzymes
Hydrolysis
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hwang, J-I., Heo, K., Shin, K. J., Kim, E., Yun, C. H. C., Ryu, S. H., ... Suh, P. G. (2000). Regulation of phospholipase C-β3 activity by Na+/H+ exchanger regulatory factor 2. Journal of Biological Chemistry, 275(22), 16632-16637. https://doi.org/10.1074/jbc.M001410200

Regulation of phospholipase C-β3 activity by Na+/H+ exchanger regulatory factor 2. / Hwang, Jong-Ik; Heo, Kyun; Shin, Kum Joo; Kim, Eunjoon; Yun, C. H Chris; Ryu, Sung Ho; Shin, Hee Sup; Suh, Pann Ghill.

In: Journal of Biological Chemistry, Vol. 275, No. 22, 02.06.2000, p. 16632-16637.

Research output: Contribution to journalArticle

Hwang, J-I, Heo, K, Shin, KJ, Kim, E, Yun, CHC, Ryu, SH, Shin, HS & Suh, PG 2000, 'Regulation of phospholipase C-β3 activity by Na+/H+ exchanger regulatory factor 2', Journal of Biological Chemistry, vol. 275, no. 22, pp. 16632-16637. https://doi.org/10.1074/jbc.M001410200
Hwang, Jong-Ik ; Heo, Kyun ; Shin, Kum Joo ; Kim, Eunjoon ; Yun, C. H Chris ; Ryu, Sung Ho ; Shin, Hee Sup ; Suh, Pann Ghill. / Regulation of phospholipase C-β3 activity by Na+/H+ exchanger regulatory factor 2. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 22. pp. 16632-16637.
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