This application contains proposals to look at several aspects of the NADPH oxidase of neutrophils. Several studies on phosphorylation will be carried out, including one on IRAK-4. An examination of the PX domain of p47PHOX will be undertaken. A complex study of cytochrome b558 and its related RaplA will be carried out. An investigation will be made of the mechanism by which 02- production is terminated will be made. A kinase-dependent system that transmits the oxidase-activating signal from the beginning to the end will be investigated. Further study will be carried out on the possibility that p67PHOX carries NADPH to the electron transport chain. Finally, X-ray crystallography of the oxidase components will be done.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024227-21
Application #
6862586
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Sawyer, Richard T
Project Start
1986-03-01
Project End
2008-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
21
Fiscal Year
2005
Total Cost
$611,825
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Johnson, Jennifer L; Brzezinska, Agnieszka A; Tolmachova, Tanya et al. (2010) Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms. Traffic 11:533-47
Brzezinska, Agnieszka A; Johnson, Jennifer L; Munafo, Daniela B et al. (2009) Signalling mechanisms for Toll-like receptor-activated neutrophil exocytosis: key roles for interleukin-1-receptor-associated kinase-4 and phosphatidylinositol 3-kinase but not Toll/IL-1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF). Immunology 127:386-97
Munafo, Daniela B; Johnson, Jennifer L; Brzezinska, Agnieszka A et al. (2009) DNase I inhibits a late phase of reactive oxygen species production in neutrophils. J Innate Immun 1:527-42
Brzezinska, Agnieszka A; Johnson, Jennifer L; Munafo, Daniela B et al. (2008) The Rab27a effectors JFC1/Slp1 and Munc13-4 regulate exocytosis of neutrophil granules. Traffic 9:2151-64
Catz, Sergio D (2008) Characterization of Rab27a and JFC1 as constituents of the secretory machinery of prostate-specific antigen in prostate carcinoma cells. Methods Enzymol 438:25-40
Munafo, Daniela B; Johnson, Jennifer L; Ellis, Beverly A et al. (2007) Rab27a is a key component of the secretory machinery of azurophilic granules in granulocytes. Biochem J 402:229-39
Pacquelet, Sandrine; Johnson, Jennifer L; Ellis, Beverly A et al. (2007) Cross-talk between IRAK-4 and the NADPH oxidase. Biochem J 403:451-61
DeLano, Frank A; Parks, Dale A; Ruedi, Julie M et al. (2006) Microvascular display of xanthine oxidase and NADPH oxidase in the spontaneously hypertensive rat. Microcirculation 13:551-66
Johnson, Jennifer L; Ellis, Beverly A; Munafo, Daniela B et al. (2006) Gene transfer and expression in human neutrophils. The phox homology domain of p47phox translocates to the plasma membrane but not to the membrane of mature phagosomes. BMC Immunol 7:28
Johnson, Jennifer L; Ellis, Beverly A; Noack, Deborah et al. (2005) The Rab27a-binding protein, JFC1, regulates androgen-dependent secretion of prostate-specific antigen and prostatic-specific acid phosphatase. Biochem J 391:699-710

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