Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors

Nature. 1996 Sep 5;383(6595):89-92. doi: 10.1038/383089a0.


Stimulation of two metabotropic glutamate-receptor subtypes, mGluR1 and mGluR5, triggers the release of Ca2+ from intracellular stores through the inositol-(1,4,5) trisphosphate (InsP3) pathway. Here we report that glutamate induces single-peaked intracellular Ca2+ mobilization in mGluR1alpha-transfected cells but elicits Ca2+ oscillations in mGluR5a-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-interacting domains of mGluR1alpha and mGluR5a, respectively. Pharmacological and peptide mapping analyses indicated that phosphorylation of the threonine residue at position 840 of mGluR5a 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.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Aspartic Acid / metabolism
  • Calcium / metabolism*
  • Cell Line
  • GTP-Binding Proteins / metabolism
  • Glutamic Acid / metabolism
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Rats
  • Receptors, AMPA / metabolism
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Threonine / metabolism
  • Transfection


  • Receptors, AMPA
  • Receptors, Metabotropic Glutamate
  • Recombinant Fusion Proteins
  • Threonine
  • Aspartic Acid
  • Glutamic Acid
  • Protein Kinase C
  • GTP-Binding Proteins
  • Calcium
  • glutamate receptor ionotropic, AMPA 1