Activation of protein kinase C by the 14-3-3 proteins homologous with Exo1 protein that stimulates calcium-dependent exocytosis.
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 Exo1, stimulates Ca(2+)-dependent exocytosis in permeabilized adrenal chromaffin cells, suggesting that this protein family may influence the protein kinase C-mediated control of Ca(2+)-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 Exo1 to reactivate Ca(2+)-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 Ca(2+)-dependent protein kinase, protein kinase C and type II calmodulin-dependent protein kinase.
Isobe
T
T
Department of Chemistry, Faculty of Science, Tokyo Metropolitan University, Japan.
Hiyane
Y
Y
Ichimura
T
T
Okuyama
T
T
Takahashi
N
N
Nakajo
S
S
Nakaya
K
K
D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D005089:Exocytosis; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014446:Tyrosine 3-Monooxygenase
D048948:14-3-3 Proteins; D002413:Cations, Divalent; D009419:Nerve Tissue Proteins; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C; D010751:Phosphopyruvate Hydratase; D002118:Calcium