The in vitro characterization of the inhibition of mouse brain protein kinase-C by retinoids and their receptors.
The mechanism of the in vitro inhibition of Ca2+-, phosphatidylserine-dependent protein kinase C (PK-C)2 by the purified holo (ligand-saturated) forms of cellular retinol-binding protein (cRBP) and cellular retinoic acid-binding protein (cRABP) was studied. We report here that the PK-C-inhibitory action of holo-cRBP and holo-cRABP is due to their respective ligands, all-trans-retinol and all-trans-retinoic acid; the reduced phosphorylation of the holo-retinoid-binding proteins and brain cytosolic proteins is not the result of a retinoid-induced soluble phosphatase or protease activity; retinoids reduce PK-C affinity for calcium and phosphatidylserine in vitro; and the structure-function activity of the retinoids and the specific interaction of these compounds with their binding proteins are important in blocking the activity of PK-C. These observations suggest that the inhibitory effect of retinoids on plasma membrane-associated PK-C activity pays a significant role in defining the early epigenetic aspects of PK-C-dependent tumor promotion and may be a physiological mechanism by which retinoids induce terminal differentiation in cell types that do not express soluble retinoid-binding proteins.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology*; D002417:Cattle; D005260:Female; D006657:Histones / Q000378:metabolism; D051379:Mice; D010718:Phosphatidylserines / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D018168:Receptors, Retinoic Acid; D012176:Retinoids / Q000494:pharmacology*; D012177:Retinol-Binding Proteins / Q000494:pharmacology*; D054840:Retinol-Binding Proteins, Cellular; D054839:Retinol-Binding Proteins, Plasma; D014212:Tretinoin / Q000494:pharmacology
D002352:Carrier Proteins; D006657:Histones; D010718:Phosphatidylserines; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D054839:Retinol-Binding Proteins, Plasma; D014212:Tretinoin; D011493:Protein Kinase C; D002118:Calcium