Effects of Newly Synthesized DCP-LA- Phospholipids on Protein Kinase C and Protein Phosphatases

Background/Aims: The linoleic acid derivative DCP-LA selectively activates PKCe and inhibits protein phosphatase 1 (PP1). In the present study, we have newly synthesized phosphatidyl-ethanolamine, -serine, -choline, and -inositol containing DCP-LA at the a and b position (diDCP-LA-PE, -PS, PC, and -PI, respectively), and examined the effects of these compounds on activities of PKC isozymes and protein phosphatases. Methods: Activities of PKC isozymes PKCa, -bI, -bII, -γ, -δ, -e-, ι, and -ζ and protein phosphatases PP1, PP2A, and protein tyrosine phosphatase 1B (PTP1B) were assayed under the cell-free conditions. Results: All the compounds activated PKC, with the different potential, but only PKCγ inhibition was obtained with diDCP-LA-PC. Of compounds diDCP-LA-PE alone significantly activated PKC ι and -ζ. diDCP-LA-PE and diDCP-LA-PI suppressed PP1 activity, but otherwise diDCP-LA-PI enhanced PP2A activity. diDCP-LA-PE, diDCP-LA-PS, and diDCP-LA-PI strongly reduced PTP1B activity, while diDCP-LA-PC enhanced the activity. Conclusion: All the newly synthesized DCP- LA-phospholipids serve as a PKC activator and of them diDCP-LA-PE alone has the potential to activate the atypical PKC isozymes PKCι and -ζ. diDCP-LA-PE and diDCP-LA-PI serve as an inhibitor for PP1 and PTP1B, diDCP-LA-PS as a PTP1B inhibitor, diDCP-LA-PI as a PP2A enhancer, and diDCP-LA-PC as a PTP1B enhancer.