Selective activation of the gamma-subspecies of protein kinase C from bovine cerebellum by arachidonic acid and its lipoxygenase metabolites.
The gamma-subspecies of protein kinase C (PKC) apparently is expressed only in central nervous tissues, and at a high level in the cerebellum and hippocampus. gamma-PKC from bovine cerebellum, but not the alpha- or beta I/beta II-subspecies, is activated by micromolar concentrations of arachidonic acid (AA), in the absence of both phospholipid and diacylglycerol. A significant component of this activation is also calcium independent. Other unsaturated fatty acids are much less active in this respect. Among the AA metabolites tested, lipoxin A (5(S),6(R),15(S)-11-cis-isomer) was a potent, selective activator of the gamma-subspecies, and also, to a lesser extent, 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid could support activation. These results raise the possibility that AA and some of its lipoxygenase metabolites may function as messenger molecules in neurones to activate the gamma-subspecies of PKC.
Shearman
M S
MS
Department of Biochemsitry, Kobe University School of Medicine, Japan.
Naor
Z
Z
Sekiguchi
K
K
Kishimoto
A
A
Nishizuka
Y
Y
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002531:Cerebellum / Q000201:enzymology*; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism*; D010743:Phospholipids / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*
D001095:Arachidonic Acids; D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D007527:Isoenzymes; D010743:Phospholipids; D016718:Arachidonic Acid; D008084:Lipoxygenase; D011493:Protein Kinase C; D002118:Calcium