title: p40phox, a third cytosolic component of the activation complex of the NADPH oxidase to contain src homology 3 domains.
abstract: The NADPH oxidase generates superoxide in phagocytic cells. It is important for immunity and its deficiency leads to chronic granulomatous disease (CGD). It consists of a membrane-bound flavocytochrome b that lies dormant until activated by the translocation to the plasma membrane of cytosolic proteins, p47phox (phox for phagocyte oxidase), p67phox and p21rac, a small GTP-binding protein. We show here that a novel component, p40phox, forms an activation complex with p47phox and p67phox with which it translocates to the membrane to associate with the flavocytochrome b. cDNA cloning and amino acid analysis revealed that p40phox has an src homology 3 (SH3) domain and a large region of sequence similarity with the N-terminus of p47phox. The primary association of p40phox appears to be with p67phox, and it is present in reduced amounts in patients with CGD lacking p67phox.
authors.affiliation: Division of Molecular Medicine, University College, London, U.K.
authors.forename: F B
authors.initials: FB
authors.lastname: Wientjes
authors.forename: J J
authors.initials: JJ
authors.lastname: Hsuan
authors.forename: N F
authors.initials: NF
authors.lastname: Totty
authors.forename: A W
authors.initials: AW
authors.lastname: Segal
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D002462:Cell Membrane / Q000201:enzymology; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004789:Enzyme Activation; D016391:Genes, src; D006105:Granulomatous Disease, Chronic / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology; D010750:Phosphoproteins / Q000032:analysis*; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D010750:Phosphoproteins; C085072:neutrophil cytosol factor 40K; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases