RGD Reference Report - Targeting of protein kinase A by muscle A kinase-anchoring protein (mAKAP) regulates phosphorylation and function of the skeletal muscle ryanodine receptor. - Rat Genome Database

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Targeting of protein kinase A by muscle A kinase-anchoring protein (mAKAP) regulates phosphorylation and function of the skeletal muscle ryanodine receptor.

Authors: Ruehr, ML  Russell, MA  Ferguson, DG  Bhat, M  Ma, J  Damron, DS  Scott, JD  Bond, M 
Citation: Ruehr ML, etal., J Biol Chem. 2003 Jul 4;278(27):24831-6. Epub 2003 Apr 21.
RGD ID: 8554839
Pubmed: PMID:12709444   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M213279200   (Journal Full-text)

Protein kinase A anchoring proteins (AKAPs) tether cAMP-dependent protein kinase (PKA) to specific subcellular locations. The muscle AKAP, mAKAP, co-localizes with the sarcoplasmic reticulum Ca2+ release channel or ryanodine receptor (RyR). The purpose of this study was to determine whether anchoring of PKA by mAKAP regulates RyR function. Either mAKAP or mAKAP-P, which is unable to anchor PKA, was expressed in CHO cells stably expressing the skeletal muscle isoform of RyR (CHO-RyR1). Immunoelectron microscopy showed that mAKAP co-localized with RyR1 in disrupted skeletal muscle. Following the addition of 10 microm forskolin to activate adenylyl cyclase, RyR1 phosphorylation in CHO-RyR1 cells expressing mAKAP increased by 42.4 +/- 6.6% (n = 4) compared with cells expressing mAKAP-P. Forskolin treatment alone did not increase the amplitude of the cytosolic Ca2+ transient in CHO-RyR1 cells expressing mAKAP or mAKAP-P; however, forskolin plus 10 mm caffeine elicited a cytosolic Ca2+ transient, the amplitude of which increased by 22% (p < 0.05) in RyR1/mAKAP-expressing cells compared with RyR1/mAKAP-P-expressing cells. Therefore, localization of PKA by mAKAP at RyR1 increases both PKA-dependent RyR phosphorylation as well as efflux of Ca2+ through the RyR. Therefore, RyR1 function is regulated by mAKAP targeting of PKA, implying an important functional role for PKA phosphorylation of RyR in skeletal muscle.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
junctional sarcoplasmic reticulum membrane located_inIDA 8554839PMID:12709444BHF-UCL 
perinuclear region of cytoplasm located_inIDA 8554839PMID:12709444BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Akap6  (A-kinase anchoring protein 6)


Additional Information