Roles of subunit phosphorylation in regulating glutamate receptor function

John Q. Wang, Ming Lei Guo, Dao Zhong Jin, Bing Xue, Eugene E. Fibuch, Li Min Mao

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Protein phosphorylation is an important mechanism for regulating ionotropic glutamate receptors (iGluRs). Early studies have established that major iGluR subtypes, including α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and N-methyl-d-aspartate (NMDA) receptors, are subject to phosphorylation. Multiple serine, threonine, and tyrosine residues predominantly within the C-terminal regions of AMPA receptor and NMDA receptor subunits have been identified as sensitive phosphorylation sites. These distinct sites undergo either constitutive phosphorylation or activity-dependent phosphorylation induced by changing cellular and synaptic inputs. An increasing number of synapse-enriched protein kinases have been found to phosphorylate iGluRs The common kinases include protein kinase A, protein kinase C, Ca 2+/calmodulin-dependent protein kinase II, Src/Fyn non-receptor tyrosine kinases, and cyclin dependent kinase-5. Regulated phosphorylation plays a well-documented role in modulating the biochemical, biophysical, and functional properties of the receptor. In the future, identifying the precise mechanisms how phosphorylation regulates iGluR activities and finding the link between iGluR phosphorylation and the pathogenesis of various brain diseases, including psychiatric and neurodegenerative diseases, chronic pain, stroke, Alzheimer's disease and substance addiction, will be hot topics and could contribute to the development of novel pharmacotherapies, by targeting the defined phosphorylation process, for suppressing iGluR-related disorders.

Original languageEnglish (US)
Pages (from-to)183-187
Number of pages5
JournalEuropean Journal of Pharmacology
Issue number1
StatePublished - Apr 5 2014


  • AMPA
  • CaMKII
  • Cdk5
  • Excitatory amino acid
  • NMDA
  • PKA
  • PKC
  • Tyrosine kinase

ASJC Scopus subject areas

  • Pharmacology


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