RGD Reference Report - Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors. - Rat Genome Database

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Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors.

Authors: Wang, J  Liu, S  Fu, Y  Wang, JH  Lu, Y 
Citation: Wang J, etal., Nat Neurosci 2003 Oct;6(10):1039-47. Epub 2003 Sep 21.
RGD ID: 734740
Pubmed: PMID:14502288   (View Abstract at PubMed)
DOI: DOI:10.1038/nn1119   (Journal Full-text)

CA1 pyramidal neurons degenerate after transient forebrain ischemia, whereas neurons in other regions of the hippocampus remain intact. Here we show that in rat hippocampal CA1 neurons, forebrain ischemia induces the phosphorylation of the N-methyl-D-aspartate (NMDA) receptor 2A subunit at Ser1232 (phospho-Ser1232). Ser1232 phosphorylation is catalyzed by cyclin-dependent kinase 5 (Cdk5). Inhibiting endogenous Cdk5, or perturbing interactions between Cdk5 and NR2A subunits, abolished NR2A phosphorylation at Ser1232 and protected CA1 pyramidal neurons from ischemic insult. Thus, we conclude that modulation of NMDA receptors by Cdk5 is the primary intracellular event underlying the ischemic injury of CA1 pyramidal neurons.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
brain ischemia  ISOCdk5 (Rattus norvegicus)734740; 734740 RGD 
brain ischemia  IMP 734740 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
peptidyl-serine phosphorylation  IDA 734740 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cyclin-dependent protein serine/threonine kinase activity  IDA 734740 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased susceptibility to ischemic brain injury  IDA 734740 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Cdk5  (cyclin-dependent kinase 5)
Grin2a  (glutamate ionotropic receptor NMDA type subunit 2A)

Genes (Mus musculus)
Cdk5  (cyclin dependent kinase 5)

Genes (Homo sapiens)
CDK5  (cyclin dependent kinase 5)

Objects referenced in this article
Gene GRIN2A glutamate ionotropic receptor NMDA type subunit 2A Homo sapiens

Additional Information