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

Nat Neurosci. 1999 Apr;2(4):331-8. doi: 10.1038/7243.

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.

Publication types

  • Research Support, Non-U.S. Gov't

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
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Phenanthridines / pharmacology
  • Phenols / pharmacology
  • Phosphorylation
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology*
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
  • Proto-Oncogene Proteins pp60(c-src) / deficiency
  • Proto-Oncogene Proteins pp60(c-src) / genetics
  • Proto-Oncogene Proteins pp60(c-src) / physiology*
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Wistar
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology*
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophosphatidic Acid
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Salicylates / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Tetradecanoylphorbol Acetate / chemistry
  • Tetradecanoylphorbol Acetate / pharmacology
  • Xenopus laevis
  • meta-Aminobenzoates

Substances

  • 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