Two novel proteins activate superoxide generation by the NADPH oxidase NOX1

Botond Bánfi, Robert A Clark, Klaus Steger, Karl Heinz Krause

Research output: Contribution to journalArticle

373 Citations (Scopus)

Abstract

NOX1, an NADPH oxidase expressed predominantly in colon epithelium, shows a high degree of similarity to the phagocyte NADPH oxidase. However, superoxide generation by NOX1 has been difficult to demonstrate. Here we show that NOX1 generates superoxide when co-expressed with the p47phox and p67phox subunits of the phagocyte NADPH oxidase but not when expressed by itself. Since p47phox and p67phox are restricted mainly to myeloid cells, we searched for their homologues and identified two novel cDNAs. The mRNAs of both homologues were found predominantly in colon epithelium. Differences between the homologues and the phagocyte NADPH oxidase subunits included the lack of the autoinhibitory domain and the protein kinase C phosphorylation sites in the p47phox homologue as well as the absence of the first Src homology 3 domain and the presence of a hydrophobic stretch in the p67phox homologue. Co-expression of NOX1 with the two novel proteins led to stimulus-independent high level superoxide generation. Stimulus dependence of NOX1 was restored when p47phox was used to replace its homologue. In conclusion, NOX1 is a superoxide-generating enzyme that is activated by two novel proteins, which we propose to name NOXO1 (NOX organizer 1) and NOXA1 (NOX activator 1).

Original languageEnglish (US)
Pages (from-to)3510-3513
Number of pages4
JournalJournal of Biological Chemistry
Volume278
Issue number6
DOIs
StatePublished - Feb 7 2003

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NADPH Oxidase
Superoxides
Phagocytes
Colon
Proteins
Epithelium
Phosphorylation
src Homology Domains
Myeloid Cells
Protein Kinase C
Names
Complementary DNA
Messenger RNA
Enzymes
neutrophil cytosol factor 67K

ASJC Scopus subject areas

  • Biochemistry

Cite this

Two novel proteins activate superoxide generation by the NADPH oxidase NOX1. / Bánfi, Botond; Clark, Robert A; Steger, Klaus; Krause, Karl Heinz.

In: Journal of Biological Chemistry, Vol. 278, No. 6, 07.02.2003, p. 3510-3513.

Research output: Contribution to journalArticle

Bánfi, Botond ; Clark, Robert A ; Steger, Klaus ; Krause, Karl Heinz. / Two novel proteins activate superoxide generation by the NADPH oxidase NOX1. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 6. pp. 3510-3513.
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