Abstract

The activation of human neutrophils is accompanied by the phosphorylation of a 48K phosphoprotein. A connection between the 48K phosphoprotein and the process of respiratory burst oxidase activation is suggested by the observations that the phosphorylation of this protein is defective in two forms of chronic granulomatous disease, a group of inherited conditions in which the respiratory burst oxidase fails to function. We propose to characterize the 48K phosphoprotein in molecular terms and in terms of its interaction with other oxidase components. Monoclonal and polyclonal antibodies against the 48K phosphoprotein will be obtained and used as probes for isolating and sequencing a cDNA clone of the protein. Once this clone is available, it will be used as a probe to study the chromosomal location of the protein as well as its expression in phagocytes. Studies will be carried out to define number and location of phosphate groups on the various isoforms of the 48K phosphoprotein. The phosphoprotein will be purified and crystallized for purposes of determining its 3-dimensional structure. Finally, we will examine interactions of the 48K phosphoprotein with other oxidase components and with detergents that activate the oxidase in the cell-free system.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI028479-02
Application #
3143018
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1989-07-01
Project End
1994-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

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

  Publications

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
Lopes, Lucia Rossetti; Dagher, Marie-Claire; Gutierrez, Abel et al. (2004) Phosphorylated p40PHOX as a negative regulator of NADPH oxidase. Biochemistry 43:3723-30
Babior, Bernard M (2004) NADPH oxidase. Curr Opin Immunol 16:42-7
Hoyal, Carolyn R; Gutierrez, Abel; Young, Brandon M et al. (2003) Modulation of p47PHOX activity by site-specific phosphorylation: Akt-dependent activation of the NADPH oxidase. Proc Natl Acad Sci U S A 100:5130-5
Catz, S D; Johnson, J L (2003) BCL-2 in prostate cancer: a minireview. Apoptosis 8:29-37
Dang, Pham My-Chan; Cross, Andrew R; Quinn, Mark T et al. (2002) Assembly of the neutrophil respiratory burst oxidase: a direct interaction between p67PHOX and cytochrome b558 II. Proc Natl Acad Sci U S A 99:4262-5
Catz, Sergio D; Johnson, Jennifer L; Babior, Bernard M (2002) The C2A domain of JFC1 binds to 3'-phosphorylated phosphoinositides and directs plasma membrane association in living cells. Proc Natl Acad Sci U S A 99:11652-7
Catz, Sergio D; Babior, Bernard M; Johnson, Jennifer L (2002) JFC1 is transcriptionally activated by nuclear factor-kappaB and up-regulated by tumour necrosis factor alpha in prostate carcinoma cells. Biochem J 367:791-9
Dang, P M; Cross, A R; Babior, B M (2001) Assembly of the neutrophil respiratory burst oxidase: a direct interaction between p67PHOX and cytochrome b558. Proc Natl Acad Sci U S A 98:3001-5
Babior, B M (2000) Phagocytes and oxidative stress. Am J Med 109:33-44

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