Regulation of muscle creatine kinase by phosphorylation in normal and diabetic hearts |
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Authors: | G Lin Y Liu K M MacLeod |
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Institution: | (1) Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada |
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Abstract: | Protein kinase C (PKC) is an important signaling molecule in the heart, but its targets remain unclear. Using a PKC substrate
antibody, we detected a 40-kDa phosphorylated cardiac protein that was subsequently identified by tandem mass spectroscopy
as muscle creatine kinase (M-CK) with phosphorylation at serine 128. The forward reaction using ATP to generate phosphocreatine
was reduced, while the reverse reaction using phosphocreatine to generate ATP was increased following dephosphorylation of
immunoprecipitated M-CK with protein phosphatase 2A (PP2A) or PP2C. Despite higher PKC levels in diabetic hearts, decreased
phosphorylation of M-CK was more prominent than the reduction in its expression. Changes in CK activity in diabetic hearts
were similar to those found following dephosphorylation of M-CK from control hearts. The decrease in phosphorylation may act
as a compensatory mechanism to maintain CK activity at an appropriate level for cytosolic ATP regeneration in the diabetic
heart.
Received 15 September 2008; received after revision 30 September 2008; accepted 13 October 2008 |
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Keywords: | " target="_blank"> Muscle creatine kinase PKC isoform phosphorylation ATP phosphocreatine |
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