Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2000 May 23;9711:6185-90. doi: 10.1073/pnas.97.11.6185.
Show Gene links
Show Anatomy links
Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: selective desensitization of the inositol trisphosphate/Ca2+ pathway by phosphorylation of the receptor-G protein-coupling domain.
Francesconi A
,
Duvoisin RM
.
???displayArticle.abstract???
Signaling by the metabotropic glutamate receptor 1alpha (mGluR1alpha) can lead to the accumulation of inositol 1,4, 5-trisphosphate (InsP(3)) and cAMP and to the modulation of K(+) and Ca(2+) channel opening. At present, very little is known about how these different actions are integrated and eventually turned off. Unraveling the molecular mechanisms underlying these functions is crucial for understanding mGluR-mediated regulation of synaptic transmission. It has been shown that receptor-induced activation of the InsP(3) pathway is subject to feedback inhibition mediated by protein kinase C (PKC). In this study, we provide evidence for a differential regulation by PKC and protein kinase A of two distinct mGluR1alpha-dependent signaling pathways. PKC activation selectively inhibits agonist-dependent stimulation of the InsP(3) pathway but does not affect receptor signaling via cAMP. In contrast, protein kinase A potentiates agonist-independent signaling of the receptor via InsP(3). Furthermore, we demonstrate that the selectivity of PKC action on receptor signaling rests on phosphorylation of a threonine residue located in the G protein-interacting domain of the receptor. Modification at Thr(695) selectively disrupts mGluR1alpha-G(q/11) interaction without affecting signaling through G(s). Together, these data provide insight on the mechanisms by which selective down-regulation of a specific receptor-dependent signaling pathway can be achieved and on how cross-talk between different second messenger cascades may contribute to fine-tune short- and long-term receptor activity.
Alaluf,
Rapid agonist mediated phosphorylation of the metabotropic glutamate receptor 1 alpha by protein kinase C in permanently transfected BHK cells.
1995, Pubmed
Alaluf,
Rapid agonist mediated phosphorylation of the metabotropic glutamate receptor 1 alpha by protein kinase C in permanently transfected BHK cells.
1995,
Pubmed
Aramori,
Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells.
1992,
Pubmed
Aronica,
Mechanisms underlying developmental changes in the expression of metabotropic glutamate receptors in cultured cerebellar granule cells: homologous desensitization and interactive effects involving N-methyl-D-aspartate receptors.
1993,
Pubmed
Balázs,
Metabotropic glutamate receptor agonists potentiate cyclic AMP formation induced by forskolin or beta-adrenergic receptor activation in cerebral cortical astrocytes in culture.
1998,
Pubmed
Bhalla,
Emergent properties of networks of biological signaling pathways.
1999,
Pubmed
Casabona,
Developmental changes in the modulation of cyclic AMP formation by the metabotropic glutamate receptor agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid in brain slices.
1992,
Pubmed
Catania,
Desensitization of metabotropic glutamate receptors in neuronal cultures.
1991,
Pubmed
Chen,
Differential regulation by cAMP-dependent protein kinase and protein kinase C of the mu opioid receptor coupling to a G protein-activated K+ channel.
1994,
Pubmed
,
Xenbase
Clapham,
G protein beta gamma subunits.
1997,
Pubmed
Conn,
Pharmacology and functions of metabotropic glutamate receptors.
1997,
Pubmed
Daaka,
Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A.
1997,
Pubmed
Duvoisin,
The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit: beta 4.
1989,
Pubmed
,
Xenbase
Ferraguti,
Activation of the extracellular signal-regulated kinase 2 by metabotropic glutamate receptors.
1999,
Pubmed
Fiorillo,
Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons.
1998,
Pubmed
Francesconi,
Role of the second and third intracellular loops of metabotropic glutamate receptors in mediating dual signal transduction activation.
1998,
Pubmed
Gereau,
Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5.
1998,
Pubmed
,
Xenbase
Gudermann,
Diversity and selectivity of receptor-G protein interaction.
1996,
Pubmed
Guérineau,
G-protein-mediated desensitization of metabotropic glutamatergic and muscarinic responses in CA3 cells in rat hippocampus.
1997,
Pubmed
Hall,
Heptahelical receptor signaling: beyond the G protein paradigm.
1999,
Pubmed
Hausdorff,
Turning off the signal: desensitization of beta-adrenergic receptor function.
1990,
Pubmed
Herrero,
Positive feedback of glutamate exocytosis by metabotropic presynaptic receptor stimulation.
1992,
Pubmed
Herrero,
Rapid desensitization of the metabotropic glutamate receptor that facilitates glutamate release in rat cerebrocortical nerve terminals.
1994,
Pubmed
Herrero,
Functional switch from facilitation to inhibition in the control of glutamate release by metabotropic glutamate receptors.
1998,
Pubmed
Ikeda,
Heterologous expression of metabotropic glutamate receptors in adult rat sympathetic neurons: subtype-specific coupling to ion channels.
1995,
Pubmed
Joly,
Molecular, functional, and pharmacological characterization of the metabotropic glutamate receptor type 5 splice variants: comparison with mGluR1.
1995,
Pubmed
,
Xenbase
Kammermeier,
Expression of RGS2 alters the coupling of metabotropic glutamate receptor 1a to M-type K+ and N-type Ca2+ channels.
1999,
Pubmed
Kawabata,
Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors.
1996,
Pubmed
Kawabata,
Diversity of calcium signaling by metabotropic glutamate receptors.
1998,
Pubmed
Lefkowitz,
G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization.
1998,
Pubmed
Li,
Angiotensin II stimulates ERK via two pathways in epithelial cells: protein kinase C suppresses a G-protein coupled receptor-EGF receptor transactivation pathway.
1998,
Pubmed
Macek,
Protein kinase C and A3 adenosine receptor activation inhibit presynaptic metabotropic glutamate receptor (mGluR) function and uncouple mGluRs from GTP-binding proteins.
1998,
Pubmed
Manzoni,
The glutamate receptor of the Qp-type activates protein kinase C and is regulated by protein kinase C.
1990,
Pubmed
McCool,
Rat group I metabotropic glutamate receptors inhibit neuronal Ca2+ channels via multiple signal transduction pathways in HEK 293 cells.
1998,
Pubmed
Nakanishi,
Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity.
1994,
Pubmed
Pearson,
Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations.
1991,
Pubmed
Pin,
The metabotropic glutamate receptors: structure and functions.
1995,
Pubmed
Pitcher,
G protein-coupled receptor kinases.
1998,
Pubmed
Prézeau,
Changes in the carboxyl-terminal domain of metabotropic glutamate receptor 1 by alternative splicing generate receptors with differing agonist-independent activity.
1996,
Pubmed
Reid,
cAMP levels increased by activation of metabotropic glutamate receptors correlate with visual plasticity.
1996,
Pubmed
Roberson,
The mitogen-activated protein kinase cascade couples PKA and PKC to cAMP response element binding protein phosphorylation in area CA1 of hippocampus.
1999,
Pubmed
Rodríguez-Moreno,
Switch from facilitation to inhibition of excitatory synaptic transmission by group I mGluR desensitization.
1998,
Pubmed
Saugstad,
RGS4 inhibits signaling by group I metabotropic glutamate receptors.
1998,
Pubmed
,
Xenbase
Schoepp,
Selective inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in the rat hippocampus by activation of protein kinase C.
1988,
Pubmed
Yu,
Membrane-delimited modulation of NMDA currents by metabotropic glutamate receptor subtypes 1/5 in cultured mouse cortical neurons.
1997,
Pubmed