PROTEIN KINASE-C-ALPHA BUT NOT PROTEIN KINASE-C-EPSILON IS DIFFERENTIALLY DOWN-REGULATED BY BRYOSTATIN-1 AND TETRADECANOYL PHORBOL 13-ACETATE IN SH-SY5Y HUMAN NEUROBLASTOMA-CELLS

SH-SY5Y human neuroblastoma cells can be induced to differentiate by phorbol esters but not by bryostatins although both agents increase protein kinase C (PKC) activity in these cells to a similar extent. We examined whether this difference could be explained by differences in the responses of specific PKC isoenzymes. Both TPA and bryostatin 1 at 10 nM induced a rapid increase in membrane-associated PKC-α immunoreactivity which was sustained for 72 hours in TPA-treated cells, but was down-regulated within 24 hours in bryostatin-treated cells. TDA likewise induced a sustained phosphorylation of an 80 kDa PKC substrate whereas in bryostatin-treated cells the 80 kDa substrate was rapidly phosphorylated reaching a maximum at 6 hours followed by a decline to basal level within 48 hours. A higher concentration of TPA (300 nM), which results in a less differentiated phenotype, induced down-regulation of PKC-α within 24 hours. In contrast, both TPA and bryostatin 1 stimulated translocation and a partial down-regulation of PKC-ε{lunate} with similar kinetics. These results suggest that the divergent actions of bryostatin I and TPA in SH-SY5Y cells are at least partially due to differential modulation of PKC-α but not PKC-ε{lunate} by these two agents. © 1993 Academic Press. All rights reserved.