Calphobindins (Placental Annexins) Inhibit Protein Kinase C

Abstract

Calphobindins (CPBs, placental annexins) are intracellular Ca²⁺- and phospholipid-dependent proteins like protein kinase C [EC 2. 7. 1. 37]. We investigated the inhibitory effects of calphobindins on the protein kinase C activity in vitro. CPB I inhibited the protein kinase C activity for both histone phosphorylation and lipocortin phosphorylation, but CPB II and CPB III inhibited only the protein kinase C activity for histone phosphorylation. In the case of histone phosphorylation, all CPBs inhibited the protein kinase C activity in a concentration-dependent manner, and the IC₅₀ (concentration required for 50% inhibition) value of CPB I was 70nM. The inhibition of protein kinase C by CPB I was Ca²⁺-dependent, and did not disappear upon increasing the concentration of phosphatidylserine. Kinetic analysis by double-reciprocal plots indicated that CPB I interacted not only with phosphatidylserine but also with protein kinase C. Although CPB I partially interacts with phospholipid, it is conceivable that the inhibitory action of CPB I on protein kinase C results from direct interaction of CPB I with protein kinase C. Since CPBs are mainly present under the plasma membrane, it is presumed that CPB I is an endogenous inhibitor of protein kinase C, and according to intracellular circumstances, CPB II and CPB III may also be endogenous inhibitors.