Arachidonic acid and diacylglycerol act synergistically to activate protein kinase C in vitro and in vivo.
Using a well-defined model membrane bilayer system, incorporation of both lipid second messengers, 1,2-diacylglycerol and arachidonic acid, at submaximal activating concentrations, resulted in a synergistic activation of protein kinase C in a Ca2+/phosphatidylserine-dependent manner as measured by monitoring phosphorylation of phosphoprotein substrates. The arachidonic acid appears to modulate membrane properties both at the hydrocarbon core and the membrane surface increasing the availability of the diacylglycerol which can bind to and subsequently activate the enzyme. Co-application of these two lipid activators to the Hermissenda photoreceptor reduced K+ channel conductance in a synergistic manner via a PKC-dependent pathway. Thus, these in vivo and in vitro studies suggest that the membrane bilayer properties of these PKC lipid activators interact to specifically regulate the cellular lipid microenvironment resulting in PKC activation.
National Institutes of Health, Section of Neural Systems, Bethesda, MD 20892.
D S
DS
Lester
C
C
Collin
R
R
Etcheberrigaray
D L
DL
Alkon
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology*; D003600:Cytosol / Q000201:enzymology; D004075:Diglycerides / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation; D007700:Kinetics; D008051:Lipid Bilayers; D008974:Mollusca; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010786:Photoreceptor Cells / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems
D004075:Diglycerides; D008051:Lipid Bilayers; D016718:Arachidonic Acid; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C