Membrane components can modulate the substrate specificity of protein kinase C.
The cationic amphiphile, cholesteryl-3 beta-carboxyamidoethylene-trimethylammonium iodide, can alter the substrate specificity of protein kinase C (PKC). The phosphorylation of histone catalyzed by PKC requires the binding of the enzyme to phospholipid vesicles. This cationic amphiphile reduces both the binding of PKC to lipid and as a consequence its rate of phosphorylation of histone. In contrast, PKC bound to large unilamellar vesicles (LUVs) composed of 50 mol% POPS, 20 mol% POPC, and 30 mol% of this amphiphile catalyzes protamine sulfate phosphorylation by an almost 4 fold greater rate. This activation requires phosphatidylserine (PS) and is inhibited by Ca2+. The extent of activation is affected by the time of incubation of PKC with LUVs. This data suggests a novel mechanism by which PKC-dependent signal transduction pathways may be altered by altering the protein targets of this enzyme.
Bruins
R H
RH
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
Epand
R M
RM
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000494:pharmacology; D002458:Cell Fractionation; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011479:Protamines / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction; D013379:Substrate Specificity; D013501:Surface-Active Agents / Q000494:pharmacology*
D006657:Histones; D008081:Liposomes; D008565:Membrane Proteins; D010743:Phospholipids; D011479:Protamines; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C076843:N,N,N-trimethyl-N'-cholesteryl amidoethyl ammonium; D002784:Cholesterol; D011493:Protein Kinase C; D002118:Calcium