Novel Human Homologues of p47phox and p67phox Participate in Activation of Superoxide-producing NADPH Oxidases

Ryu Takeya, Noriko Ueno, Keiichiro Kami, Masahiko Taura, Motoyuki Kohjima, Tomoko Izaki, Hiroyuki Nunoi, Hideki Sumimoto

Research output: Contribution to journalArticle

305 Citations (Scopus)

Abstract

The catalytic core of a superoxide-producing NADPH oxidase (Nox) in phagocytes is gp91phox/Nox2, a membrane-integrated protein that forms a heterodimer with p22phox to constitute flavocytochrome b 558. The cytochrome becomes activated by interacting with the adaptor proteins p47phox and p67phox as well as the small GTPase Rac. Here we describe the cloning of human cDNAs for novel proteins homologous to p47phox and p67phox, designated p41 nox and p51nox, respectively; the former is encoded by NOXO1 (Nox organizer 1), and the latter is encoded by NOXA1 (Nox activator 1). The novel homologue p41nox interacts with p227phox via the two tandem SH3 domains, as does p47phox. The protein p51 nox as well as p67phox can form a complex with p47 phox and with p41nox via the C-terminal SH3 domain and binds to GTP-bound Rac via the N-terminal domain containing four tetratricopeptide repeat motifs. These bindings seem to play important roles, since p47phox and p67phox activate the phagocyte oxidase via the same interactions. Indeed, p41nox and p51nox are capable of replacing the corresponding classical homologue in activation of gp91phox. Nox1, a homologue of gp91phox, also can be activated in cells, when it is coexpressed with p41nox and p51 nox, with p41nox and p67phox, or with p47 phox and p51nox; in the former two cases, Nox1 is partially activated without any stimulants added, suggesting that p41 nox is normally in an active state. Thus, the novel homologues p41nox and p51nox likely function together or in combination with a classical one, thereby activating the two Nox family oxidases.

Original languageEnglish
Pages (from-to)25234-25246
Number of pages13
JournalJournal of Biological Chemistry
Volume278
Issue number27
DOIs
Publication statusPublished - Jul 4 2003

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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