Interaction of palmitoylcarnitine with protein kinase C in neuroblastoma NB-2a cells.
As reported previously [Acta Neurobiol. Exp. 57 (1997) 263], palmitoylcarnitine was observed to promote differentiation of neuroblastoma NB-2a cells with a concomitant inhibition of proliferation and of the phorbol ester stimulated activity of the protein kinase C (PKC). In the present study, palmitoylcarnitine was observed to inhibit phosphorylation of the PKC peptide substrate and to completely diminish binding of phorbol 12-myristate-13-acetate (PMA), although the effect was found to be uncompetitive. The exposure of NB-2a cells to palmitoylcarnitine in the presence of PMA resulted in a dramatic decrease in phosphorylation of the conventional and novel isozymes of PKC, mainly on serine. This effect was observed to be dose dependent. Inhibitors of serine/threonine phosphatases were not influencing the effect of palmitoylcarnitine what can point to an interaction between PKC and palmitoylcarnitine, affecting the process of autophosphorylation. These findings suggest that pamitoylcarnitine could be a natural modulator of PKC activity, thus regulating the process of cell differentiation.
Sobiesiak-Mirska
Joanna
J
Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Pasteur Street 3, 02-093 Warsaw, Poland.
Nałecz
Maciej J
MJ
Nałecz
Katarzyna A
KA
D000818:Animals; D002454:Cell Differentiation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009447:Neuroblastoma / Q000201:enzymology* / Q000473:pathology; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010172:Palmitoylcarnitine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate