Abstract

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.

  Funding Agency

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

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

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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