Role for the first SH3 domain of p67phox in activation of superoxide-producing NADPH oxidases
Role for the first SH3 domain of p67phox in activation of superoxide-producing NADPH oxidases
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DOI：
10.1016/j.bbrc.2008.12.112
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发表时间：
2009-02-06
影响因子：
3.1
通讯作者：
Surnimoto, Hideki
中科院分区：
文献类型：
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作者：
Maehara, Yuichi;Miyano, Kei;Surnimoto, Hideki
吞噬细胞中的膜结合NADPH氧化酶gp91（phox）。Nox2)产生超氧化物，这是杀微生物氧化剂的前体，因此在宿主防御中起着至关重要的作用。gp91(phox)/ Nox2的激活需要与细胞质蛋白p67（phox）和p47（phox）组装，每一个都包含两个SH3结构域。虽然p67（phox）的c端SH3结构域负责与p47（phox）结合，但对第一个（N端）SH3结构域的作用知之甚少[SH3(N)]。在这里，我们发现p67(phox)-SH3(N)的截断，而不是精氨酸取代SH3(N)中不变残基Trp-277，导致gp91(phox)/Nox2的激活受损。这种损伤被细胞中SH3(N)缺陷p67（phox）的高表达所掩盖，这表明SH3(N)主要增加了p67（phox）对氧化酶复合物的亲和力。另一方面，p67(phox)-SH3(N)不参与gp91(phox)/Nox2密切相关的同源物Nox1和Nox3的激活。因此，p67(phox)-SH3(N)可能通过促进氧化酶组装特异性地激活gp91(phox)/Nox2。(C) 2009爱思唯尔公司版权所有。
The membrane-bound NADPH oxidase in phagocytes, gp91(phox)(a.k.a. Nox2), produces Superoxide, a precursor of microbicidal oxidants, thereby playing a Crucial role in host defense. Activation of gp91(phox)/ Nox2 requires assembly with the cytosolic proteins p67(phox) and p47(phox), each containing two SH3 domains. Although the C-terminal SH3 domain of p67(phox) is responsible for binding to p47(phox), little is known about the role for the first (N-terminal) SH3 domain [SH3(N)]. Here we show that truncation of p67(phox)-SH3(N), but not Substitution of arginine for the invariant residue Trp-277 in SH3(N), results in an impaired activation of gp91(phox)/Nox2. The impairment is overcorne by higher expression of an SH3(N)-defective p67(phox) in cells, Suggesting that SH3(N) primarily increases the affinity of p67(phox) for the oxidase complex. On the other hand, p67(phox)-SH3(N) is not involved in activation of Nox1 and Nox3, closely-related homologues of gp91(phox)/Nox2. Thus p67(phox)-SH3(N) specifically functions in gp91(phox)/Nox2 activation probably via facilitating oxidase assembly. (C) 2009 Elsevier Inc. All rights reserved.