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Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors

Abstract

STIMULATION of two metabotropic glutamate-receptor subtypes, mGluRl and mGluRS, triggers the release of Ca2+ from intra-cellular stores through the inositol-(1,4,5) trisphosphate (InsP3) pathway1,3. Here we report that glutamate induces single-peaked intracellular Ca2+ mobilization in mGluR1α-transfected cells but elicits Ca2+ oscillations in mGluRSa-transfected cells. The response patterns of the intracellular Ca2+ increase depend upon the identity of a single amino acid, aspartate (at position 854) or threonine (at position 840), located within the G-protein-inter-acting domains of mGluR1α and mGluR5a, respectively. Pharmacological and peptide mapping analyses indicated that phosphorylation of the threonine residue at position 840 of mGluRSa by protein kinase C (PKC) is responsible for the generation of Ca2+ oscillations in mGluR5a-expressing cells. To our knowledge this is the first evidence that PKC phosphorylation of G-protein-coupled receptors is important in producing oscillations in intracellular Ca2+ signalling.

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Kawabata, S., Tsutsumi, R., Kohara, A. et al. Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors. Nature 383, 89–92 (1996). https://doi.org/10.1038/383089a0

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