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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Hematology Subcommittee 2 (HEM)
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Scripps Research Institute
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