Signal transduction in human monocytes: relationship between superoxide production and the level of kinase C in the membrane.
Activation of monocytes and neutrophils results in an increased production of superoxide, an important cytotoxic compound. The previous finding that two agents that induce superoxide production cause opposite translocation of kinase C (Costa-Casnellie et al. [1985] Biochem. Biophys. Res. Commun., 133:1139-1144). led us to study the role of kinase C in superoxide production. In monocytes induction of superoxide production by 13-tetradecanoate phorbol acetate requires translocation of kinase C from the cytosol to the membrane. Superoxide production is also induced by concanavalin A, but this induction is accompanied by a shift of kinase C from the membrane to the cytosol. Superoxide production by concanavalin A is greatly augmented by cytochalasin B. During activation by Con A and cytochalasin B the membrane kinase C is translocated to the cytosol in a manner similar to that observed in the presence of Con A alone. Under these conditions approximately 5-10% of kinase C remains associated with the membrane. Thus, induction of superoxide production by concanavalin A is independent of the levels of kinase C tightly bound to the membrane. We also show evidence that the concanavalin A-induced release of kinase C from the membrane is not due to an increase in levels of intracellular calcium or increased phosphoinositide turnover. In summary, these data indicate that concanavalin A and phorbol ester-induced superoxide production by human monocytes occurs by distinct pathways and that superoxide production is not closely correlated with specific levels of membrane-associated kinase C activity.
D002462:Cell Membrane / Q000201:enzymology; D003208:Concanavalin A / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000097:blood*; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003208:Concanavalin A; D013481:Superoxides; D003571:Cytochalasin B; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate