Inhibition of the Ca2+- and phospholipid-dependent protein kinase by a novel Mr 17,000 Ca2+-binding protein.

A novel Mr 17,000 Ca2+-binding protein isolated from bovine brain was found to be a potent inhibitor of the Ca2+- and phospholipid-dependent protein kinase (protein kinase C), also isolated from bovine brain. Half-maximal inhibition by this calciprotein of the initial rate of phosphorylation of histone III-S by protein kinase C occurred at a calciprotein concentration of 2.2 microM under standard conditions. Comparison of the effects of a number of Ca2+-binding proteins on protein kinase C activity indicated that the Mr 17,000 Ca2+-binding protein was the most potent inhibitor, followed by the intestinal Ca2+-binding protein and calcineurin. Calmodulin, troponin C, S-100 protein and a Mr 21,000 Ca2+-binding protein of bovine brain were relatively weak inhibitors of protein kinase C. The inhibitory effect of the Mr 17,000 Ca2+-binding protein was apparently not due to its interaction with phospholipid or the basic protein substrate and therefore appears to be due to a direct effect on the protein kinase C. These observations suggest that the novel Mr 17,000 Ca2+-binding protein, and possibly other Ca2+-binding proteins, may play a physiological role in regulating the activity of protein kinase C.