Evidence for a Direct and Functional Interaction between the Regulators of G Protein Signaling-2 and Phosphorylated C Terminus of Cholecystokinin-2 Receptor

Ingrid Langer, Irina G. Tikhonova, Cyril Boulegue, Jean-Pierre Esteve, Sebastien Vatinel, Audrey Ferrand, Luis Moroder, Patrick Robberecht, Daniel Fourmy

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Signaling of G protein-coupled receptors (GPCRs) is regulated by different mechanisms. One of these involves regulators of G protein signaling (RGS), which are diverse and multifunctional proteins that bind to active G alpha subunits of G proteins and act as GTPase-activating proteins. Little is known about the molecular mechanisms that govern the selective use of RGS proteins in living cells. We first demonstrated that CCK2R-mediated inositol phosphate production, known to be G(q-)dependent, is more sensitive to RGS2 than to RGS4 and is insensitive to RGS8. Both basal and agonist-stimulated activities of the CCK2R are regulated by RGS2. By combining biochemical functional, and in silico structural approaches, we demonstrate that a direct and functional interaction occurs between RGS2 and agonist-stimulated cholecystokinin receptor-2 (CCK2R) and identified the precise residues involved: phosphorylated Ser434 and Thr439 located in the C-terminal tail of CCK2R and Lys62, Lys63, and Gln67, located in the N-terminal domain of RGS2. These findings confirm previous reports that RGS proteins can interact with GPCRs to modulate their signaling and provide a molecular basis for RGS2 recognition by the CCK2R.

Original languageEnglish
Pages (from-to)502-513
Number of pages12
JournalMolecular Pharmacology
Volume75
Issue number3
DOIs
Publication statusPublished - Mar 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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