CONTROL OF CALCIUM OSCILLATIONS BY PHOSPHORYLATION OF METABOTROPIC GLUTAMATE RECEPTORS

STIMULATION of two metabotropic glutamate-receptor subtypes, mGluR1 an d mGluR5, triggers the release of Ca2+ from intracellular stores throu gh the inositol-(1,4,5)trisphosphate (InsP(3)) pathway(1-3). Here rye report that glutamate induces single-peaked intracellular Ca2+ mobiliz ation in mGluR1 alpha-transfected cells but elicits Ca2+ oscillations in mGluR5a-transfected cells, The response patterns of the intracellul ar Ca2+ increase depend upon the identity of a single amino acid, aspa rtate (at position 854) or threonine (at position 840), located within the G-protein-interacting domains of mGluR1 alpha and mGluR5a, respec tively, Pharmacological and peptide mapping analyses indicated that ph osphorylation of the threonine residue at position 840 of mGluR5a by p rotein kinase C (PKC) is responsible for the generation of Ca2+ oscill ations in mGluR5a-expressing cells, To our knowledge this is the first evidence that PKC phosphorylation of G-protein-coupled receptors is i mportant in producing oscillations in intracellular Ca2+ signalling.