Cloning of a 67-kD Neutrophil Oxidase Factor with Similarity to a Noncatalytic Region of p60 c-src

作者：Thomas L. Leto, Karen J. Lomax, Bryan D. Volpp, Hiroyuki Nunoi, Joan M. G. Sechler, William Michael Nauseef, Robert Alfred Clark, John I. Gallin, Harry L. Malech · 发表于：Science · 年份：1990 · DOI：10.1126/science.1692159 · 被引用次数：388 · 研究领域：Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Neuroinflammation and Neurodegeneration Mechanisms、Redox biology and oxidative stress

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.