Evidence for a direct and functional interaction between the regulators of G protein signaling-2 and phosphorylated C terminus of cholecystokinin-2 receptor.

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 Galpha 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.
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Molecular Pharmacology, American Society for Pharmacology and Experimental Therapeutics, 2009, 75 (3), pp.502-13. 〈10.1124/mol.108.051607〉
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Contributeur : Marie Francoise Simon <>
Soumis le : lundi 3 août 2009 - 09:32:14
Dernière modification le : samedi 6 octobre 2018 - 13:16:01

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Ingrid Langer, Irina Tikhonova, Cyril Boulègue, Jean-Pierre Estève, Sébastien Vatinel, et al.. Evidence for a direct and functional interaction between the regulators of G protein signaling-2 and phosphorylated C terminus of cholecystokinin-2 receptor.. Molecular Pharmacology, American Society for Pharmacology and Experimental Therapeutics, 2009, 75 (3), pp.502-13. 〈10.1124/mol.108.051607〉. 〈inserm-00408743〉

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