CTP:phosphocholine cytidylyltransferase and protein kinase C recognize different physical features of membranes: differential responses to an oxidized phosphatidylcholine.
Protein kinase C (PKC) and CTP:phosphocholine cytidylyltransferase (CT) are two examples of enzymes that are regulated by reversible binding to membranes, and this binding is influenced by membrane physical properties. CT activation by oxidized phosphatidylcholines was recently demonstrated and was linked to the acyl chain disordering effect of the oxidized species (Biochemistry 38, 15606). In this paper, we compare the responses of PKC and CT to an oxidized PC, and investigate the physical properties of lipid bilayers that modulate the activity of these enzymes. We show that 1-palmitoyl, 2-(11,15 dihydroxy) eicosatrienoyl PC (diOH-PAPC) caused less of an increase in the temperature of the lamellar to hexagonal II transition (T(H)) of an unsaturated PE, compared to its parent, PAPC. Using a polarity-sensitive interfacial probe, we also found evidence to suggest that this oxidized PC increases interfacial packing pressure. We found that whereas diOH-PAPC activates CT, it inhibits PKC relative to the parent PAPC. The activities of both CT and PKC are known to increase in the presence of non-lamellar forming lipids. The greater activating effect of diOH-PAPC compared with PAPC, is consistent with a stimulation of the activity of CT by negative curvature strain. However, this is not the case with PKC, for which we suggest that surface packing pressure is of prime importance.
Drobnies
Adrienne E
AE
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Davies
Sarah M A
SM
Kraayenhof
Ruud
R
Epand
Raquel F
RF
Epand
Richard M
RM
Cornell
Rosemary B
RB
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D019916:Choline-Phosphate Cytidylyltransferase / Q000378:metabolism*; D003911:Dextrans; D004789:Enzyme Activation / Q000187:drug effects; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D008081:Liposomes; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008567:Membranes, Artificial; D008954:Models, Biological; D009173:Mycophenolic Acid / Q000031:analogs & derivatives*; D010084:Oxidation-Reduction; D010742:Phospholipid Ethers / Q000737:chemistry / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; D003911:Dextrans; D005456:Fluorescent Dyes; D008081:Liposomes; D008563:Membrane Lipids; D008567:Membranes, Artificial; D010742:Phospholipid Ethers; C050527:dextran T70-mycophenolic acid conjugate; D011493:Protein Kinase C; D019916:Choline-Phosphate Cytidylyltransferase; D009173:Mycophenolic Acid