Phorbol myristate acetate mediates redistribution of protein kinase C in human neutrophils: potential role in the activation of the respiratory burst enzyme.
Protein kinase C may be important in leukocyte function, because it is activated by phorbol myristate acetate (PMA), a potent stimulus of the respiratory burst in neutrophils. The localization of protein kinase C was compared in unstimulated and PMA-stimulated human neutrophils. Protein kinase C was primarily cytosolic in unstimulated cells but became associated with the particulate fraction after treatment of cells with PMA. The particulate-associated kinase activity did not require added calcium and lipids, but when extracted by Triton X-100 (greater than or equal to 0.2%), calcium and phospholipid dependence could be demonstrated. The EC50 of PMA for stimulating kinase redistribution and activation of NADPH oxidase, the respiratory burst enzyme, were similar (30 to 40 nM). Redistribution of protein kinase C occurred rapidly (no lag) and preceded NADPH oxidase activation (30 sec lag). These results suggest that redistribution of protein kinase C is linked to activation of the respiratory burst in human neutrophils.
Wolfson
M
M
McPhail
L C
LC
Nasrallah
V N
VN
Snyderman
R
R
D000469:Alkaline Phosphatase / Q000378:metabolism; D002451:Cell Compartmentation; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D010101:Oxygen Consumption; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011494:Protein Kinases; D011493:Protein Kinase C; D000469:Alkaline Phosphatase; D013755:Tetradecanoylphorbol Acetate