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1,2-diacylglycerols, but not phorbol esters, activate a potential inhibitory pathway for protein kinase C in GH/sub 3/ pituitary cells

Journal Article · · J. Biol. Chem.; (United States)
OSTI ID:6838397
;
It has been suggested that sphingoid bases may serve as physiologic inhibitors of protein kinase C. Because 1,2-diacylglycerols, but not phorbol esters, enhance sphingomyelin degradation via a sphingomyelinase in GH/sub 3/ pituitary cells, the effects of phorbol esters, 1,2-diacylglycerols, and sphingomyelinase on protein kinase C activation were assessed. Under basal conditions, the inactive cytosolic form of protein kinase C predominated. 1,2-Diacylglycerols stimulated transient protein kinase C redistribution to the membrane. 1.2-Dioctanoylglycerol (200 ..mu..g/ml) reduced cytosolic protein kinase C activity to 67% of control. In contrast, the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), stimulated redistribution to the membrane without return to the cytosol. Exogenous sphingomyelinase reduced membrane-bound protein kinase C activity to 30% of control, yet did not alter cytosolic activity. Sphingomyelinase, added after phorbol ester-induced redistribution was completed, restored activity to the cytosol. These studies suggest that a pathway involving a sphingomyelinase might comprise a physiologic negative effector system for protein kinase C. Further, the failure of phorbol esters to activate this system might account for some differences between these agents.
Research Organization:
Univ. Medical College, New York, NY (USA)
OSTI ID:
6838397
Journal Information:
J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 263:14; ISSN JBCHA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
CARCINOGENS
CELL CONSTITUENTS
CELL MEMBRANES
CYTOPLASM
DAYS LIVING RADIOISOTOPES
ENDOCRINE GLANDS
ENZYME INDUCTION
ENZYMES
ESTERS
GENE REGULATION
GLANDS
GLYCEROL
HYDROXY COMPOUNDS
ISOTOPES
KINETICS
LIGHT NUCLEI
MEMBRANES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHORBOL ESTERS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PITUITARY GLAND
RADIOISOTOPES
REACTION KINETICS
TRANSFERASES