The effect of membrane fluidization on protein kinase C: Inhibition by ethanol and higher alcohols and stimulation by increased lipid unsaturation or addition non-esterified fatty acids
- Thomas Jefferson Univ., Philadelphia, PA (United States)
Protein kinase C (PKC) is a membrane bound enzyme that is dependent on calcium, anionic phospholipids, and sn-1,2-diacylglycerol (DAG) to be fully active. The relationship between membrane fluidity and PKC activity was investigated using model vesicle systems composed of phosphatidylserine alone or in combination with phosphatidylcholine. Effects on membrane fluidity were assessed using the fluorescence anisotropy of diphenylhexatriene. When membrane fluidity was increased by the addition of short chain n-alkanols, PKC activity was inhibited. There was a linear relationship for a given level of inhibition and the membrane-buffer partition coefficient. By contrast, when the degree of unsaturation in the phosphatidylcholine was increased, although the bilayer was again fluidized, PKC activity was enhanced. The addition of non-esterified fatty acid also activated PKC, either when directly added to the vesicles or when generated by the addition of exogenous phospholipase A[sub 2], and again the bilayer was fluidized. It is proposed that a more fluid membrane lipid bilayer, induced by increased unsaturation or non-esterified fatty acids, facilitated optimal interaction at the DAG site since the effect could be demonstrated in a lipid free system using protamine sulfate.
- OSTI ID:
- 6894244
- Report Number(s):
- CONF-9202109--
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Vol. 6:1; ISSN FAJOEC; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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ALCOHOLS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
ENZYME ACTIVITY
ENZYMES
ESTERS
ETHANOL
HYDROXY COMPOUNDS
INHIBITION
KINETICS
LIPIDS
MEMBRANES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
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PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PROTEINS
REACTION KINETICS
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