CLONING OF A 67-KD NEUTROPHIL OXIDASE FACTOR WITH SIMILARITY TO A NONCATALYTIC REGION OF P60C-SRC
CLONING OF A 67-KD NEUTROPHIL OXIDASE FACTOR WITH SIMILARITY TO A NONCATALYTIC REGION OF P60C-SRC
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DOI：
10.1126/science.1692159
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发表时间：
1990-05-11
期刊：
影响因子：
56.9
通讯作者：
MALECH, HL
中科院分区：
文献类型：
--
作者：
LETO, TL;LOMAX, KJ;MALECH, HL
慢性肉芽肿性疾病（CGD）的特征是由吞噬细胞（还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶）产生的超氧化物受损引起的复发性感染。克隆了编码67千道尔顿（kD）细胞溶质氧化酶因子（p67）的互补DNA，该因子在5%的CGD患者中缺乏。重组p67（r-p67）部分恢复NADPH氧化酶活性p67缺陷的中性粒细胞胞质溶胶从这些患者。p67 cDNA编码一个526个氨基酸的蛋白质，其酸性中间和羧基末端结构域与src相关酪氨酸激酶的非催化结构域中发现的序列基序相似。最近在磷脂酶C-γ、非红细胞α-血影蛋白（fodrin）、p21 ras-鸟苷三磷酸酶激活蛋白（GAP）、肌球蛋白-1亚型、酵母蛋白cdc-25和fus-1以及47-kD吞噬细胞氧化酶因子（p47）中发现了这种基序，这表明可能存在共同的调控特征。
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 ofsrc-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.