Cloning of a 67-kD neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src.
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-gamma, nonerythroid alpha-spectrin (fodrin), p21ras-guanosine triphophatase-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.
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
T L
TL
Leto
K J
KJ
Lomax
B D
BD
Volpp
H
H
Nunoi
J M
JM
Sechler
W M
WM
Nauseef
R A
RA
Clark
J I
JI
Gallin
H L
HL
Malech
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000097:blood / Q000235:genetics*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016392:Proto-Oncogene Proteins pp60(c-src); D012689:Sequence Homology, Nucleic Acid
D011518:Proto-Oncogene Proteins; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)