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Calmodulin-dependent multiprotein kinase and protein kinase C phosphorylate and inactivate both intact, microsomal HMG-CoA reductase, and the purified 53 kDa catalytic fragment. Isolation of the single phosphopeptide produced by combined cleavage with cyanogen bromide and Lys-C proteinase reveals that this is due to phosphorylation of a single serine residue near the C-terminus, corresponding to serine-872...
We have previously shown that incubation of isolated hepatocytes with fructose leads to elevation of AMP and activation of the AMP-activated protein kinase. We now show that this treatment causes marked inactivation of HMG-CoA reductase. Using immunoprecipitation from the microsomal fraction of 32 P-labelled cells, we also show that this treatment leads to a 2.6-fold increase in the phosphorylation...
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