Activation of protein kinase C by the 14‐3‐3 proteins homologous with Exol protein that stimulates calcium‐dependent exocytosis

Abstract

The 14‐3‐3 proteins are a family of acidic proteins found mainly in the brain and are suggested to have a role in monoamine synthesis based on their ability to activate tyrosine and tryptophan hydroxylases in the presence of type II Ca²⁺/calmodulin‐dependent protein kinase. Recently, however, it has been demonstrated that a member of the 14‐3‐3 family, termed Exol, stimulates Ca²⁺‐dependent exocytosis in permeabilized adrenal chromaffin cells, suggesting that this protein family may influence the protein kinase C‐mediated control of Ca²⁺‐dependent exocytosis. Here we show that the 14‐3‐3 proteins activate protein kinase C at about 2‐fold more than the known level of the activated protein kinase, i.e. the activity of protein kinase C in the presence of Ca²⁺ and phospholipids. This raises the possibility that the cellular activity of protein kinase C is regulated by diverse members of the 14‐3‐3 family and that the reported ability of Exol to reactivate Ca²⁺‐dependent exocytosis is based on its stimulatory effect on protein kinase C activity. The 14‐3‐3 family, therefore, appears to be a multifunctional regulator of cell signalling processes mediated by two types of Ca²⁺‐dependent protein kinase, protein kinase C and type II calmodulin‐dependent protein kinase.