Protein Kinase A Increases Type-2 Inositol 1,4,5-Trisphosphate Receptor Activity by Phosphorylation of Serine 937*
AUTOR(ES)
Betzenhauser, Matthew J.
FONTE
American Society for Biochemistry and Molecular Biology
RESUMO
Protein kinase A (PKA) phosphorylation of inositol 1,4,5-trisphosphate receptors (InsP3Rs) represents a mechanism for shaping intracellular Ca2+ signals following a concomitant elevation in cAMP. Activation of PKA results in enhanced Ca2+ release in cells that express predominantly InsP3R2. PKA is known to phosphorylate InsP3R2, but the molecular determinants of this effect are not known. We have expressed mouse InsP3R2 in DT40-3KO cells that are devoid of endogenous InsP3R and examined the effects of PKA phosphorylation on this isoform in unambiguous isolation. Activation of PKA increased Ca2+ signals and augmented the single channel open probability of InsP3R2. A PKA phosphorylation site unique to the InsP3R2 was identified at Ser937. The enhancing effects of PKA activation on this isoform required the phosphorylation of Ser937, since replacing this residue with alanine eliminated the positive effects of PKA activation. These results provide a mechanism responsible for the enhanced Ca2+ signaling following PKA activation in cells that express predominantly InsP3R2.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2757215Documentos Relacionados
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