A region C-terminal to the proline-rich core of p47phox regulates activation of the phagocyte NADPH oxidase by interacting with the C-terminal SH3 domain of p67phox
A region C-terminal to the proline-rich core of p47phox regulates activation of the phagocyte NADPH oxidase by interacting with the C-terminal SH3 domain of p67phox
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DOI：
10.1016/j.abb.2005.10.012
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发表时间：
2005-12-15
影响因子：
3.9
通讯作者：
Sumimoto, H
中科院分区：
文献类型：
--
作者：
Mizuki, K;Takeya, R;Sumimoto, H
吞噬细胞NADPH氧化酶的激活需要调节蛋白p47（phox）和p67（phox），每个都含有两个SH 3结构域。p67（phox）与p47（phox）通过p67（phox）C-末端SH 3结构域同时结合氨基酸残基360-369的脯氨酸富集区（PRR）及其p47（phox）C-末端侧翼区而相互作用;相互作用在氧化酶调节中的作用尚未完全理解。在这里，我们表明，p47（phox）-p67（phox）的相互作用不仅被破坏的PRR的删除，但也被替换为额外的PRR（K383 E/K385 E）的碱性残基。取代受损氧化酶激活部分在体外和更深刻的体内，表明的意义的p47（phox）额外的PRR。替代的Ser-379在extra-PRR，一个残基已知在刺激的细胞中进行磷酸化，由天冬氨酸减弱的相互作用，从而导致在一个有缺陷的超氧化物的生产，这表明磷酸化的Ser-379参与氧化酶的调节。(c)2005年爱思唯尔公司All rights reserved.
Activation of the phagocyte NADPH oxidase requires the regulatory proteins p47(phox) and p67(phox), each harboring two SH3 domains. p67(phox) interacts with p47(phox) via simultaneous binding of the p67(phox) C-terminal SH3 domain to both the proline-rich region (PRR) of amino acid residues 360-369 and its C-terminally flanking region of p47(phox); the role of the interaction in oxidase regulation has not been fully understood. Here we show that the p47(phox)-p67(phox) interaction is disrupted not only by deletion of the PRR but also by substitution for basic residues in the extra-PRR (K383E/K385E). The substitution impaired oxidase activation partially in vitro and much more profoundly in vivo, indicating the significance of the p47(phox) extra-PRR. Replacement of Ser-379 in the extra-PRR, a residue known to undergo phosphorylation in stimulated cells, by aspartate attenuates the interaction and thus results in a defective superoxide production, suggesting that phosphorylation of Ser-379 is involved in oxidase regulation. (c) 2005 Elsevier Inc. All rights reserved.