Phosphorylation of serine-880 in GluR2 by protein kinase C prevents its C terminus from binding with glutamate receptor-interacting protein

J Neurochem. 1999 Oct;73(4):1765-8. doi: 10.1046/j.1471-4159.1999.731765.x.


Phosphorylation of the glutamate receptor is an important mechanism of synaptic plasticity. Here, we show that the C terminus of GluR2 of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor is phosphorylated by protein kinase C and that serine-880 is the major phosphorylation site. This phosphorylation also occurs in human embryonic kidney (HEK) cells by addition of 12-O-tetradecanoylphorbol 13-acetate. Our immunoprecipitation experiment revealed that the phosphorylation of serine-880 in GluR2 drastically reduced the affinity for glutamate receptor-interacting protein (GRIP), a synaptic PDZ domain-containing protein, in vitro and in HEK cells. This result suggests that modulation of serine-880 phosphorylation in GluR2 controls the clustering of AMPA receptors at excitatory synapses and consequently contributes to synaptic plasticity.

MeSH terms

  • Amino Acid Sequence
  • Antibodies
  • Binding Sites
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Line
  • Humans
  • Immunoblotting
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Kinase C / metabolism*
  • Receptors, AMPA / metabolism
  • Receptors, Metabotropic Glutamate / chemistry
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Serine*
  • Synapses / physiology
  • Transfection


  • Antibodies
  • Carrier Proteins
  • GRIP1 protein, human
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Receptors, AMPA
  • Receptors, Metabotropic Glutamate
  • Recombinant Proteins
  • metabotropic glutamate receptor 2
  • Phosphoserine
  • Serine
  • Protein Kinase C