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Dissociation of Rac translocation from p47 phox /p67 phox movements in human neutrophils by tyrosine kinase inhibitors
Author(s) -
Dorseuil Olivier,
Quinn Mark T.,
Bokoch Gary M.
Publication year - 1995
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.58.1.108
Subject(s) - biology , tyrosine kinase , chromosomal translocation , microbiology and biotechnology , dissociation (chemistry) , kinase , protein tyrosine kinases , tyrosine , signal transduction , biochemistry , chemistry , gene
Cytosolic components of the phagocyte NADPH oxidase (p47 phox , p67 phox , and Rac2) translocate to the plasma membrane on cell activation where they interact with a membrane‐bound cytochrome b to generate superoxide anion. Phosphorylation reactions are known to be important for activity of NADPH oxidase. Translocation of Rac2, p47 phox , and p67 phox were all enhanced in formyl‐Met‐Leu‐Phe‐stimulated neutrophils treated with 50 nM of the protein phosphatase 1/2A inhibitor calyculin A. Rac translocation was blocked by the tyrosine kinase inhibitors genistein (50 μM) and herbimycin (17 μM), whereas movement of p47 phox and p67 phox were not inhibited. Cell‐free analysis of Rac translocation also demonstrated that translocation of p47 phox and p67 phox were not linked to the movement or availability of Rac2. Thus, Rac2 does not appear to regulate NADPH oxidase by controlling movements of the cytosolic components to the membrane‐associated enzyme but may exert its effect at the level of the assembled complex. Tyrosine kinase activity is required for translocation of Rac in the chemoattractant‐stimulated human neutrophil. J. Leukoc. Biol. 58: 108–113; 1995.