Phosphorylation of microsomal HMG CoA reductase increases susceptibility to proteolytic degradation in vitro.
Conversion of native, 97-100 kDa rat liver microsomal HMG CoA reductase to membrane-bound 62 kDa and soluble 52-56 kDa catalytically active forms was catalyzed in vitro by the calcium-dependent, leupeptin- and calpastatin-sensitive protease calpain-II purified from rat liver cytosol. Cleavage of the native 97-100 kDa reductase was enhanced by pretreatment (inactivation) of microsomes with ATP(Mg2+) and liver reductase kinase (compared to protein phosphatase-pretreated controls). This was reflected in a loss of the 97-100 kDa species and an increase in the soluble 52-56 kDa species (total enzyme activity and specific immunoblot recovery).
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002154:Calpain; D002792:Cholestyramine Resin / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D010450:Endopeptidases / Q000378:metabolism*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D051381:Rats
D002792:Cholestyramine Resin; D006903:Hydroxymethylglutaryl CoA Reductases; D010450:Endopeptidases; D002154:Calpain; D002118:Calcium