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

Research output: Contribution to journalArticle

285 Citations (Scopus)

Abstract

Chronic granulomatous diseases (CGDs) are characterized by recurrent infections resulting from impaired superoxide production by a phagocytic cell, nicotinamide adeninc 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 carboxy-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
StatePublished - May 11 1990
Externally publishedYes

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Chronic Granulomatous Disease
NADPH Oxidase
Phagocytes
Organism Cloning
Oxidoreductases
Neutrophils
Complementary DNA
Spectrin
Fungal Proteins
Niacinamide
src-Family Kinases
Guanosine
Type C Phospholipases
Myosins
Superoxides
Cytosol
Protein Isoforms
Proteins
Phosphates
Amino Acids

ASJC Scopus subject areas

  • General

Cite this

Leto, T. L., Lomax, K. J., Volpp, B. D., Nunoi, H., Sechler, J. M. G., Nauseef, W. M., ... 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.

Cloning of a 67-kD neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src . / Leto, Thomas L.; Lomax, Karen J.; Volpp, Bryan D.; Nunoi, Hiroyuki; Sechler, Joan M G; Nauseef, William M.; Clark, Robert A; Gallin, John I.; Malech, Harry L.

In: Science, Vol. 248, No. 4956, 11.05.1990, p. 727-730.

Research output: Contribution to journalArticle

Leto, TL, Lomax, KJ, Volpp, BD, Nunoi, H, Sechler, JMG, Nauseef, WM, Clark, RA, Gallin, JI & Malech, HL 1990, 'Cloning of a 67-kD neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src ', Science, vol. 248, no. 4956, pp. 727-730.
Leto TL, Lomax KJ, Volpp BD, Nunoi H, Sechler JMG, Nauseef WM et al. Cloning of a 67-kD neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src Science. 1990 May 11;248(4956):727-730.
Leto, Thomas L. ; Lomax, Karen J. ; Volpp, Bryan D. ; Nunoi, Hiroyuki ; Sechler, Joan M G ; Nauseef, William M. ; Clark, Robert A ; Gallin, John I. ; Malech, Harry L. / Cloning of a 67-kD neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src In: Science. 1990 ; Vol. 248, No. 4956. pp. 727-730.
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N2 - Chronic granulomatous diseases (CGDs) are characterized by recurrent infections resulting from impaired superoxide production by a phagocytic cell, nicotinamide adeninc 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 carboxy-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.

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