Cloning of a 67-kD Neutrophil Oxidase Factor with Similarity to a Noncatalytic Region of p60
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Leto, Thomas L.; Lomax, Karen J.; Volpp, Bryan D.; Nunoi, Hiroyuki; Sechler, Joan M. G.; Nauseef, William M.; Clark, Robert A.; Gallin, John I.; Malech, Harry L.

doi:10.1126/science.1692159

Cited by 385 publications

(162 citation statements)

References 31 publications

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“…The most common cause of CCDs is an X-linked inheritance, resulting in the deficiency of the large /3 subunit of flavocytochrome b (gp91Ph0"). In approximately 3 U O % of cases, however, autosomally inherited deficiencies of other subunits with masses 47k and 67k (p47phox, and p67pho") lead to CCD (Clark et al, 1989;Let0 et al, 1990). Stimulation of neutrophils or other phagocytes results in these two cytosolic proteins, along with the small GTPases Racl or Rac2, translocating to the plasma membrane; subsequently, they form the functional NADPH oxidase, in complex with the transmembrane and heterodimeric gp9 Iphox-p22phox flavocytochrome b5S8.…”

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confidence: 99%

Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3‐kinases: Binding partners of SH3 domains?

1996

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Two SH3 domain-containing cytosolic components of the NADPH oxidase, p47ph0" and p40phox, are shown by analyses of their sequences to contain single copies of a novel class of domain, the PX (phox) domain. Homologous domains are demonstrated to be present in the Cpk class of phosphatidylinositol 3-kinase, S. cerevisiae Bemlp, and S. pombe Scd2, and a large family of human sorting nexin 1 (SNXI) homologues. The majority of these domains contains a polyproline motif, typical of SH3 domain-binding proteins. Two further findings are reported. A third NADPH oxidase subunit, p67pho", is shown to contain four tetratricopeptide repeats (TPRs) within its N-terminal RacIGTPbinding region, and a 28 residue motif in p40phox is demonstrated to be present in protein kinase C isoforms ~l h and 5; and in three ZZ domain-containing proteins.Keywords: homology; signal transduction; chronic granulomatous disease; tetratrico peptide repeats; phospholipase D Patients with chronic granulomatous diseases (CCDs) are severely predisposed to infection by fungi and bacteria due to deficiencies of the component subunits of NADPH oxidase. Dysfunction of the oxidase reduces superoxide generation, thereby compromising a major non-specific host defense mechanism of phagocytes (reviewed in Segal, 1989). The most common cause of CCDs is an X-linked inheritance, resulting in the deficiency of the large /3 subunit of flavocytochrome b (gp91Ph0"). In approximately 3 U O % of cases, however, autosomally inherited deficiencies of other subunits with masses 47k and 67k (p47phox, and p67pho") lead to CCD (Clark et al., 1989;Let0 et al., 1990). Stimulation of neutrophils or other phagocytes results in these two cytosolic proteins, along with the small GTPases Racl or Rac2, translocating to the plasma membrane; subsequently, they form the functional NADPH oxidase, in complex with the transmembrane and heterodimeric gp9 Iphox-p22phox flavocytochrome b5S8. This is the minimum complex required to generate the microbicidal superoxide anion. An additional cytosolic factor, p40pho", is known also to associate with the NADPH oxidase complex (Wientjes et al., 1993), although its regulatory roles remain uncertain.P40PhoX, p47phox, and p67phoX each contain Src homology 3 (SH3) domains, which mediate multiple associations with proline-rich targets within the NADPH oxidase complex (Fuchs et al., 1995;de Mendez et al., 1996). These domains are also present in a diverse range of kinases, phosphatases, phospholipases, and cytoskeletal proteins, and bind left-handed polyproline type I1 helices (reviewed in Pawson, 1995). The presence of other domain types in p47ph0" and p67phox, however, has not previously been noted. Here I report the identification of a novel domain family that includes p40phox, p47phox, phosphatidylinositol (PtdIns) 3-kinases, homologues of a sorting nexin (SNXI), and several yeast proteins, including the SH3-containing protein, Bemlp. 1 also record the presence of tetratricopeptide repeats (TPRs) in p67pho", and note that a 28 residue (oct...

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confidence: 99%

Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3‐kinases: Binding partners of SH3 domains?

1996

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“…Increased gp91 phox message was consistently detected in the TF1 phox /pSR␣ transfectants in comparison with control pSR␣ transfectants. To investigate whether TF1 phox overexpression was specifically affecting gp91 phox expression or was inducing differentiation and therefore causing increased gp91 phox message indirectly, the blots were probed for p47 phox (30), p67 phox (31), and CD18 (32) messages. All of these messages increase during terminal myeloid differentiation, similar to gp91 phox .…”

Section: Ifn-␥ Induces Changes In the Protein Complexes Thatmentioning

confidence: 99%

Identification and Characterization of TF1phox, a DNA-binding Protein That Increases Expression of gp91phox in PLB985 Myeloid Leukemia Cells

Eklund

Kakar

1997

Journal of Biological Chemistry

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The CYBB gene encodes gp91 phox , the heavy chain of the phagocyte-specific NADPH oxidase. CYBB is transcriptionally inactive until the promyelocyte stage of myelopoiesis, and in mature phagocytes, expression of gp91 phox is further increased by interferon-␥ (IFN-␥) and other inflammatory mediators. The CYBB promoter region contains several lineage-specific cis-elements involved in the IFN-␥ response. We screened a leukocyte cDNA expression library for proteins able to bind to one of these cis-elements (؊214 to ؊262 base pairs) and identified TF1 phox , a protein with sequence-specific binding to the CYBB promoter. Electrophoretic mobility shift assay with nuclear proteins from a variety of cell lines demonstrated binding of a protein to the CYBB promoter that was cross-immunoreactive with TF1 phox . DNA binding of this protein was increased by IFN-␥ treatment in the myeloid cell line PLB985, but not in the non-myeloid cell line HeLa. Overexpression of recombinant TF1 phox in PLB985 cells increased endogenous gp91 phox message abundance, but did not lead to cellular differentiation. Overexpression of TF1 phox in myeloid leukemia cell lines increased reporter gene expression from artificial promoter constructs containing CYBB promoter sequence. These data suggested that TF1 phox increased expression of gp91 phox .

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“…In previous studies, we found that HoxA10 represses transcription of the genes encoding two phagocyte respiratory burst oxidase proteins: gp91 PHOX and p67 PHOX (the CYBB and NCF2 genes, respectively) (20,21). These genes are actively transcribed after the promyelocyte stage of myelopoiesis, and transcription continues until cell death (22,23).…”

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Activation of SHP2 Protein-tyrosine Phosphatase Increases HoxA10-induced Repression of the Genes Encoding gp91PHOX and p67PHOX

Lindsey

Huang

Wang

et al. 2007

Journal of Biological Chemistry

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The CYBB and NCF2 genes encode the phagocyte oxidase proteins gp91 PHOX and p67 PHOX , respectively. These genes are transcribed after the promyelocyte stage of differentiation, and transcription continues until cell death. In undifferentiated myeloid cells, homologous cis-elements in the CYBB and NCF2 genes are repressed by the homeodomain transcription factor HoxA10. During cytokine-induced myelopoiesis, tyrosine phosphorylation of HoxA10 decreases binding affinity for the CYBB and NCF2 ciselements. This abrogates HoxA10-induced transcriptional repression as differentiation proceeds. Therefore, mechanisms involved in differentiation stage-specific HoxA10 tyrosine phosphorylation are of interest because HoxA10 phosphorylation modulates myeloid-specific gene transcription. In this study, we found that HoxA10 is a substrate for SHP2 protein-tyrosine phosphatase in undifferentiated myeloid cells. In contrast, HoxA10 is a substrate for a constitutively active mutant form of SHP2 in both undifferentiated and differentiating myeloid cells. Expression of such SHP2 mutants results in persistent HoxA10 repression of CYBB and NCF2 transcription during myelopoiesis. Both HoxA10 overexpression and activating SHP2 mutations have been described in human myeloid malignancies. Therefore, our results suggest that these mutations could cooperate, leading to decreased myeloidspecific gene transcription and functional differentiation block in myeloid cells with both defects.

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Cloning of a 67-kD Neutrophil Oxidase Factor with Similarity to a Noncatalytic Region of p60 ^c-src

Cited by 385 publications

References 31 publications

Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3‐kinases: Binding partners of SH3 domains?

Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3‐kinases: Binding partners of SH3 domains?

Identification and Characterization of TF1phox, a DNA-binding Protein That Increases Expression of gp91phox in PLB985 Myeloid Leukemia Cells

Activation of SHP2 Protein-tyrosine Phosphatase Increases HoxA10-induced Repression of the Genes Encoding gp91PHOX and p67PHOX

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Cloning of a 67-kD Neutrophil Oxidase Factor with Similarity to a Noncatalytic Region of p60 c-src

Cited by 385 publications

References 31 publications

Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3‐kinases: Binding partners of SH3 domains?

Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3‐kinases: Binding partners of SH3 domains?

Identification and Characterization of TF1phox, a DNA-binding Protein That Increases Expression of gp91phox in PLB985 Myeloid Leukemia Cells

Activation of SHP2 Protein-tyrosine Phosphatase Increases HoxA10-induced Repression of the Genes Encoding gp91PHOX and p67PHOX

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Cloning of a 67-kD Neutrophil Oxidase Factor with Similarity to a Noncatalytic Region of p60 ^c-src