PROTEIN-KINASE-C INHIBITORS, H7 AND CALPHOSTIN-C, INHIBIT INDUCTION OF DNA-SYNTHESIS BY CYTOSOLIC EXTRACTS OF EXPONENTIALLY GROWING NEUROBLASTOMA-CELLS IN ISOLATED-NUCLEI

Cytoplasmic extracts from proliferating Neuro-2a cells contain a prote in factor, ADR (activator of DNA replication) that induces DNA synthes is in isolated quiescent nuclei. Cytoplasmic extracts derived from qui escent-made Neuro-2a cells contain none or very little ADR activity, b ut this activity can be generated after a brief exposure of cytosolic extracts to a membrane-enriched fraction derived from exponentially gr owing Neuro-2a cells. ADR activity appears at the beginning of the S p hase of the cell cycle. Moreover it appears to be a protease, because aprotinin inhibits ADR activity. ADR activity can be also inhibited by the protein kinase C inhibitors, 1-(5-isoquinoline-sulfonyl)-2-methyl piperazine (H7) and calphostin C.