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PMID: 10204539 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors.

Nature neuroscience ·Vol. 2 ·No. 4 ·1999-04-00 ·Pages 331-8

Lu WY, Xiong ZG, Lei S, Orser BA, Dudek E, Browning MD, MacDonald JF

Abstract

The N-methyl-D-aspartate (NMDA) receptor contributes to synaptic plasticity in the central nervous system and is both serine-threonine and tyrosine phosphorylated. In CA1 pyramidal neurons of the hippocampus, activators of protein kinase C (PKC) as well as the G-protein-coupled receptor ligands muscarine and lysophosphatidic acid enhanced NMDA-evoked currents. Unexpectedly, this effect was blocked by inhibitors of tyrosine kinases, including a Src required sequence and an antibody selective for Src itself. In neurons from mice lacking c-Src, PKC-dependent upregulation was absent. Thus, G-protein-coupled receptors can regulate NMDA receptor function indirectly through a PKC-dependent activation of the non-receptor tyrosine kinase (Src) signaling cascade.

MeSH Terms
Alkaloids Amino Acid Sequence Animals Benzophenanthridines Cells, Cultured Enzyme Activation/drug effects Enzyme Inhibitors/pharmacology GTP-Binding Proteins/physiology Genistein/pharmacology Isoflavones/pharmacology Lysophospholipids/pharmacology Mice Mice, Knockout Microinjections Molecular Sequence Data Muscarine/pharmacology Nerve Tissue Proteins/physiology Neuronal Plasticity Oocytes/drug effects,metabolism Patch-Clamp Techniques Phenanthridines/pharmacology Phenols/pharmacology Phosphorylation Protein Kinase C/antagonists & inhibitors,physiology Protein Processing, Post-Translational Proto-Oncogene Proteins pp60(c-src)/antagonists & inhibitors,deficiency,genetics,physiology Pyramidal Cells/drug effects,physiology Rats Rats, Wistar Receptors, Cell Surface/drug effects,physiology Receptors, G-Protein-Coupled Receptors, Lysophosphatidic Acid Receptors, Muscarinic/drug effects,physiology Receptors, N-Methyl-D-Aspartate/physiology Salicylates/pharmacology Signal Transduction/drug effects,physiology Tetradecanoylphorbol Acetate/chemistry,pharmacology Xenopus laevis meta-Aminobenzoates
Chemicals
Alkaloids Benzophenanthridines Enzyme Inhibitors Isoflavones Lysophospholipids Nerve Tissue Proteins Phenanthridines Phenols Receptors, Cell Surface Receptors, G-Protein-Coupled Receptors, Lysophosphatidic Acid Receptors, Muscarinic Receptors, N-Methyl-D-Aspartate Salicylates meta-Aminobenzoates lavendustin B lavendustin A daidzein Muscarine Genistein chelerythrine Proto-Oncogene Proteins pp60(c-src) Protein Kinase C GTP-Binding Proteins Tetradecanoylphorbol Acetate
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lu W Y
Department of Physiology, University of Toronto, Canada.
Xiong Z G
Lei S
Orser B A
Dudek E
Browning M D
MacDonald J F
Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1097-6256
Published
1999-04-00
Pages
331-8
Language
English
Region
United States
NLM ID
9809671
Subset
IM
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