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Characterization of a Ca/sup 2 +/, calmodulin-dependent protein kinase which is able to phosphorylate native and protease cleaved purified hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6832430
; ;

The authors have extensively purified a low molecular weight Ca/sup 2 +/, calmodulin-dependent protein kinase from rat brain cytosol. This kinase (M/sub r/ 120,000) is able to phosphorylate both native and soluble purified HMG-CoA reductase. The concomitant inactivation and phosphorylation of purified HMG-CoA reductase was completely dependent on Ca/sup 2 +/ and calmodulin. Incubation of phosphorylated /sup 32/P-HMG-CoA reductase was associated with the loss of /sup 32/P-radioactivity and reactivation of inactive enzyme. Maximal phosphorylation of purified HMG-CoA reductase involved the introduction of approximately 0.5 mol phosphate/53,000 enzyme fragment. The apparent Km for purified HMG-CoA reductase was .045 mg/ml. Microsomal native HMG-CoA reductase (M/sub r/ 100,000) was also phosphorylated and inactivated following incubation with calmodulin stimulated kinase, calmodulin, Ca/sup 2 +/ and Mg-ATP; dephosphorylation (reactivation) was catalyzed by the phosphoprotein phosphatase. The isolation and characterization of the M/sub r/ 120,000 calmodulin-binding enzyme complex provides additional insights into the mechanisms of the Ca/sup 2 +/ dependent regulation of HMG-CoA reductase phosphorylation. Based on these data and the authors previous in vitro and in vivo studies, they now propose that HMG-CoA reductase activity is modulated by three separate kinase systems.

Research Organization:
National Institutes of Health, Bethesda, MD
OSTI ID:
6832430
Report Number(s):
CONF-8606151-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BODY
BRAIN
CALCIUM COMPOUNDS
CATIONS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CHARGED PARTICLES
CHEMICAL REACTIONS
COENZYMES
DAYS LIVING RADIOISOTOPES
ENZYME REACTIVATION
ENZYMES
FRACTIONATION
FUNCTIONS
IONS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MICROSOMES
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES