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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-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
Country of Publication:
United States
Language:
English

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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
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DAYS LIVING RADIOISOTOPES
ENZYME REACTIVATION
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FUNCTIONS
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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
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RADIOISOTOPES
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REACTION KINETICS
RODENTS
SEPARATION PROCESSES
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES