INVOLVEMENT OF PROTEIN-KINASE-C IN NERVE GROWTH-FACTOR-STIMULATED ANDK-252A-STIMULATED CALCIUM-UPTAKE INTO PC12 CELLS

Both nerve growth factor (NGF) and K-252a stimulate the uptake of calc ium into PC12 cells, Stimulation by either is prevented by pretreatmen t of the cells with the tumor promoter phorbol 12-myristate 13-acetate (PMA), suggesting an involvement of protein kinase C in the stimulati on, The effect of PMA is specific in that the calcium uptake stimulate d by either the L-type channel agonist BAY K 8644 or by ATP is not alt ered in PMA-pretreated cells, An involvement of kinase C is also sugge sted by the inhibition of NGF- or K-252a-stimulated calcium uptake by the kinase C inhibitors staurosporine and calphostin C, Inhibition by the isoform-specific agents GO 6976 and thymeleatoxin implicates one o f the classic calcium-sensitive isoforms of kinase C, The close simila rity in the profiles of inhibition of NGF-stimulated and K-252a-stimul ated calcium uptake by the various effecters suggests that NGF and K-2 52a act on calcium uptake through some of the same signaling elements. (C) 1997 Wiley-Liss, Inc.