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Phorbol myristate acetate induces neutrophil NADPH‐oxidase activity by two separate signal transduction pathways: dependent or independent of phosphatidylinositol 3‐kinase
Author(s) -
Karlsson Anna,
Nixon Jennifer B.,
McPhail Linda C.
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.67.3.396
Subject(s) - wortmannin , nadph oxidase , protein kinase c , superoxide , signal transduction , biology , phosphatidylinositol , kinase , microbiology and biotechnology , phorbol , biochemistry , protein kinase a , reactive oxygen species , enzyme
The neutrophil NADPH‐oxidase can be activated by protein kinase C (PKC) agonists such as phorbol myristate acetate (PMA), resulting in superoxide anion release. This superoxide release is independent of phosphatidylinositol 3‐kinase (PI 3‐kinase) because the inhibitor wortmannin does not affect the response. In this study, PMA is shown to also induce a wortmannin‐sensitive NADPH‐oxidase activation, however, not resulting in release of superoxide but in intracellular production of the radical. This indicates that two pools of NADPH‐oxidase, one localized in the plasma membrane and the other in the granule membranes, are separately regulated and the signal transduction pathways leading to activation of these pools differ regarding involvement of PI 3‐kinase. Activation of both pools was dependent on ERK/MAPK kinase (MEK) activity and protein phosphatase 1 and/or 2A. As the two oxidase responses were differently affected by the inhibitor Gö‐6850, different PKC isozymes are suggested to take part in the two signal transduction pathways. J. Leukoc. Biol. 67: 396–404; 2000.