Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors.
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.
Kawabata
S
S
Neuroscience & Gastrointestinal Research Laboratory, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd, Ibaraki, Japan.
Tsutsumi
R
R
Kohara
A
A
Yamaguchi
T
T
Nakanishi
S
S
Okada
M
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014162:Transfection
D001224:Aspartic Acid; D002118:Calcium; D019204:GTP-Binding Proteins; D018698:Glutamic Acid; D011493:Protein Kinase C; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D011993:Recombinant Fusion Proteins; D013912:Threonine