Phosphorylation of threonine 154 in p40phox is an important physiological signal for activation of the neutrophil NADPH oxidase.
Phosphorylation of threonine 154 in p40phox is an important physiological signal for activation of the neutrophil NADPH oxidase.
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苏氨酸154在p40phox中的磷酸化是激活中性粒细胞NADPH氧化酶的重要生理信号。
DOI：
10.1182/blood-2010-08-300889
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发表时间：
2010-12-23
期刊：
影响因子：
20.3
通讯作者：
Hawkins PT
中科院分区：
文献类型：
--
作者：
Chessa TA;Anderson KE;Hu Y;Xu Q;Rausch O;Stephens LR;Hawkins PT
嗜中性粒细胞烟酰胺腺嘌呤二核苷酸磷酸氧化酶是一种多亚基酶（包括gp 91 phox、p22 phox、p67 phox、p40 phox、p47 phox和Rac），在微生物杀灭中起重要作用。最近发现的慢性肉芽肿病患者表达突变型p40 phox亚基，以及小鼠模型的p40 phox功能的发展，表明磷脂酰肌醇3-磷酸结合p40 phox的PX结构域是氧化酶激活的重要信号。然而，p40 phox中其他保守残基和结构域的存在表明该蛋白质具有进一步的调节作用。为了验证这一点，我们通过逆转录病毒转导p40 phox −/−骨髓祖细胞并在辐射嵌合体中重新增殖骨髓室，将野生型和突变型p40 phox引入完全分化的小鼠中性粒细胞中。磷酸化p40 phox的苏氨酸154，而不是丝氨酸315，需要充分的氧化酶激活，以响应甲酰化的细菌肽fMLP，血清调理的金黄色葡萄球菌，和免疫球蛋白调理的绵羊红细胞。一个功能性的SH 3结构域是不需要氧化酶激活，和删除整个域导致增强氧化酶反应。蛋白激酶Cδ介导的苏氨酸154磷酸化是p47 phox完全转运到吞噬体所必需的。这些结果定义了一个重要的新元素在氧化酶的生理激活。
The neutrophil nicotinamide adenine dinucleotide phosphate-oxidase is a multisubunit enzyme (comprising gp91phox, p22phox, p67phox, p40phox, p47phox, and Rac) that plays a vital role in microbial killing. The recent discovery of a chronic granulomatous disease patient who expresses a mutant p40phox subunit, together with the development of mouse models of p40phox function, indicate phosphatidylinositol 3-phosphate binding to the PX domain of p40phox is an important signal for oxidase activation. However, the presence of other conserved residues and domains in p40phox suggest further regulatory roles for this protein. To test this, we introduced wild-type and mutated versions of p40phox into fully differentiated mouse neutrophils by retroviral transduction of p40phox−/− bone marrow progenitors and repopulation of the bone marrow compartment in radiation chimaeras. Phosphorylation of p40phox on threonine 154, but not serine 315, was required for full oxidase activation in response to formylated bacterial peptide fMLP, serum-opsonized S aureus, and immunoglobulin-opsonized sheep red blood cells. A functional SH3 domain was not required for oxidase activation, and deletion of the entire domain resulted in enhanced oxidase responses. Phosphorylation of threonine 154 in response to S aureus was mediated by protein kinase Cδ and was required for full translocation of p47phox to phagosomes. These results define an important new element in the physiological activation of the oxidase.
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影响因子：
4.4
作者：
Cheng, Ni;He, Rong;Ye, Richard D.
通讯作者：
Ye, Richard D.
影响因子：
21.3
作者：
Kanai, F;Liu, H;Yaffe, MB
通讯作者：
Yaffe, MB
影响因子：
2.9
作者：
Fontayne, A;Dang, PMC;El Benna, J
通讯作者：
El Benna, J
影响因子：
5.5
作者：
Kim, C;Dinauer, MC
通讯作者：
Dinauer, MC
DOI：
10.1186/1476-9433-3-1
发表时间：
2004-03-29
期刊：
Medical immunology (London, England)
影响因子：
--
作者：
Feng, Biao;Cheng, Shuhua;Liou, Hsiou-Chi
通讯作者：
Liou, Hsiou-Chi