Role for the first SH3 domain of p67phox in activation of superoxide-producing NADPH oxidases

Yuichi Maehara; Kei Miyano; Hideki Sumimoto

doi:10.1016/j.bbrc.2008.12.112

Role for the first SH3 domain of p67^phox in activation of superoxide-producing NADPH oxidases

Yuichi Maehara
, Kei Miyano
, Hideki Sumimoto

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

Abstract

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 overcome 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.

Original language	English
Pages (from-to)	589-593
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	379
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2008.12.112
Publication status	Published - Feb 6 2009

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2008.12.112

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@article{4c36550ab2c346179fa59f620e94aebc,

title = "Role for the first SH3 domain of p67phox in activation of superoxide-producing NADPH oxidases",

abstract = "The membrane-bound NADPH oxidase in phagocytes, gp91phox (a.k.a. Nox2), produces superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. Activation of gp91phox/Nox2 requires assembly with the cytosolic proteins p67phox and p47phox, each containing two SH3 domains. Although the C-terminal SH3 domain of p67phox is responsible for binding to p47phox, little is known about the role for the first (N-terminal) SH3 domain [SH3(N)]. Here we show that truncation of p67phox-SH3(N), but not substitution of arginine for the invariant residue Trp-277 in SH3(N), results in an impaired activation of gp91phox/Nox2. The impairment is overcome by higher expression of an SH3(N)-defective p67phox in cells, suggesting that SH3(N) primarily increases the affinity of p67phox for the oxidase complex. On the other hand, p67phox-SH3(N) is not involved in activation of Nox1 and Nox3, closely-related homologues of gp91phox/Nox2. Thus p67phox-SH3(N) specifically functions in gp91phox/Nox2 activation probably via facilitating oxidase assembly.",

keywords = "NADPH oxidase, Nox1, Nox2, Nox3, SH3 domain, gp91, p40, p47, p67",

author = "Yuichi Maehara and Kei Miyano and Hideki Sumimoto",

note = "Funding Information: We are grateful to Yohko Kage (Kyushu University and JST), Natsuko Yoshiura (Kyushu University and JST), and Namiko Kubo (Kyushu University) for technical assistance, and to Minako Nishino (Kyushu University and JST) for secretarial assistance. This work was supported in part by Grants-in-Aid for Scientific Research and Targeted Proteins Research Program (TPRP) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and by CREST of JST (Japan Science and Technology Agency).",

year = "2009",

month = feb,

day = "6",

doi = "10.1016/j.bbrc.2008.12.112",

language = "English",

volume = "379",

pages = "589--593",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier B.V.",

number = "2",

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TY - JOUR

T1 - Role for the first SH3 domain of p67phox in activation of superoxide-producing NADPH oxidases

AU - Maehara, Yuichi

AU - Miyano, Kei

AU - Sumimoto, Hideki

N1 - Funding Information: We are grateful to Yohko Kage (Kyushu University and JST), Natsuko Yoshiura (Kyushu University and JST), and Namiko Kubo (Kyushu University) for technical assistance, and to Minako Nishino (Kyushu University and JST) for secretarial assistance. This work was supported in part by Grants-in-Aid for Scientific Research and Targeted Proteins Research Program (TPRP) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and by CREST of JST (Japan Science and Technology Agency).

PY - 2009/2/6

Y1 - 2009/2/6

N2 - The membrane-bound NADPH oxidase in phagocytes, gp91phox (a.k.a. Nox2), produces superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. Activation of gp91phox/Nox2 requires assembly with the cytosolic proteins p67phox and p47phox, each containing two SH3 domains. Although the C-terminal SH3 domain of p67phox is responsible for binding to p47phox, little is known about the role for the first (N-terminal) SH3 domain [SH3(N)]. Here we show that truncation of p67phox-SH3(N), but not substitution of arginine for the invariant residue Trp-277 in SH3(N), results in an impaired activation of gp91phox/Nox2. The impairment is overcome by higher expression of an SH3(N)-defective p67phox in cells, suggesting that SH3(N) primarily increases the affinity of p67phox for the oxidase complex. On the other hand, p67phox-SH3(N) is not involved in activation of Nox1 and Nox3, closely-related homologues of gp91phox/Nox2. Thus p67phox-SH3(N) specifically functions in gp91phox/Nox2 activation probably via facilitating oxidase assembly.

AB - The membrane-bound NADPH oxidase in phagocytes, gp91phox (a.k.a. Nox2), produces superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. Activation of gp91phox/Nox2 requires assembly with the cytosolic proteins p67phox and p47phox, each containing two SH3 domains. Although the C-terminal SH3 domain of p67phox is responsible for binding to p47phox, little is known about the role for the first (N-terminal) SH3 domain [SH3(N)]. Here we show that truncation of p67phox-SH3(N), but not substitution of arginine for the invariant residue Trp-277 in SH3(N), results in an impaired activation of gp91phox/Nox2. The impairment is overcome by higher expression of an SH3(N)-defective p67phox in cells, suggesting that SH3(N) primarily increases the affinity of p67phox for the oxidase complex. On the other hand, p67phox-SH3(N) is not involved in activation of Nox1 and Nox3, closely-related homologues of gp91phox/Nox2. Thus p67phox-SH3(N) specifically functions in gp91phox/Nox2 activation probably via facilitating oxidase assembly.

KW - NADPH oxidase

KW - Nox1

KW - Nox2

KW - Nox3

KW - SH3 domain

KW - gp91

KW - p40

KW - p47

KW - p67

UR - https://www.scopus.com/pages/publications/58149479248

UR - https://www.scopus.com/pages/publications/58149479248#tab=citedBy

U2 - 10.1016/j.bbrc.2008.12.112

DO - 10.1016/j.bbrc.2008.12.112

M3 - Article

C2 - 19116138

AN - SCOPUS:58149479248

SN - 0006-291X

VL - 379

SP - 589

EP - 593

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

Role for the first SH3 domain of p67^phox in activation of superoxide-producing NADPH oxidases

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