Cloning of a 67-kD neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src

Thomas L. Leto, Karen J. Lomax, Bryan D. Volpp, Hiroyuki Nunoi, Joan M.G. Sechler, William M. Nauseef, Robert A. Clark, John I. Gallin, Harry L. Malech

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Abstract

Chronic granulomatous diseases (CGDs) are characterized by recurrent infections resulting from impaired superoxide production by a phagocytic cell, nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) oxidase. Complementary DNAs were cloned that encode the 67-kilodalton (kD) cytosolic oxidase factor (p67), which is deficient in 5% of CGD patients. Recombinant p67 (r-p67) partially restored NADPH oxidase activity to p67-deficient neutrophil cytosol from these patients. The p67 cDNA encodes a 526-amino acid protein with acidic middle and carboxyl-terminal domains that are similar to a sequence motif found in the noncatalytic domain of src-related tyrosine kinases. This motif was recently noted in phospholipase C-γ, nonerythroid α-spectrin (fodrin), p21ras-guanosine triphosphatase-activating protein (GAP), myosin-1 isoforms, yeast proteins cdc-25 and fus-1, and the 47-kD phagocyte oxidase factor (p47), which suggests the possibility of common regulatory features.

Original languageEnglish (US)
Pages (from-to)727-730
Number of pages4
JournalScience
Volume248
Issue number4956
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

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    Leto, T. L., Lomax, K. J., Volpp, B. D., Nunoi, H., Sechler, J. M. G., Nauseef, W. M., Clark, R. A., Gallin, J. I., & Malech, H. L. (1990). Cloning of a 67-kD neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src. Science, 248(4956), 727-730. https://doi.org/10.1126/science.1692159