RGD Reference Report - A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1. - Rat Genome Database

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A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1.

Authors: Jeske, NA  Diogenes, A  Ruparel, NB  Fehrenbacher, JC  Henry, M  Akopian, AN  Hargreaves, KM 
Citation: Jeske NA, etal., Pain. 2008 Sep 15;138(3):604-16. Epub 2008 Apr 1.
RGD ID: 2313201
Pubmed: PMID:18381233   (View Abstract at PubMed)
PMCID: PMC2593399   (View Article at PubMed Central)
DOI: DOI:10.1016/j.pain.2008.02.022   (Journal Full-text)

Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-kinase anchoring protein (AKAP). On nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results in the sensitization to many different stimuli, contributing to the development of hyperalgesia. In this study, we investigated the functional involvement of AKAP150 in mediating sensitization of TRPV1, and found that AKAP150 is co-expressed in trigeminal ganglia (TG) neurons from rat and associates with TRPV1. Furthermore, siRNA-mediated knock-down of AKAP150 expression led to a significant reduction in PKA phosphorylation of TRPV1 in cultured TG neurons. In CHO cells, the PKA RII binding site on AKAP was necessary for PKA enhancement of TRPV1-mediated Ca2+-accumulation. In addition, AKAP150 knock-down in cultured TG neurons attenuated PKA sensitization of TRPV1 activity and in vivo administration of an AKAP antagonist significantly reduced prostaglandin E2 sensitization to thermal stimuli. These data suggest that AKAP150 functionally regulates PKA-mediated phosphorylation/sensitization of the TRPV1 receptor.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of calcium ion transport into cytosol  IDA 2313201 RGD 
positive regulation of protein phosphorylation  IMP 2313201PKARGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPIAkap5 (Rattus norvegicus)2313201 RGD 
protein kinase binding  IPIPrkaca (Rattus norvegicus)2313201 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Akap5  (A-kinase anchoring protein 5)
Prkaca  (protein kinase cAMP-activated catalytic subunit alpha)


Additional Information