Papers - TAKEYA Ryu
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Regulation of superoxide-producing NADPH oxidases in nonphagocytic cells.
Takeya R, Ueno N, Sumimoto H
Methods in enzymology 406 456 - 68 2006
Language：Japanese Publishing type：Research paper (scientific journal)
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Mizuki K., Takeya R., Kuribayashi F., Nobuhisa I., Kohda D., Nunoi H., Takeshige K., Sumimoto H.
Archives of Biochemistry and Biophysics 444 ( 2 ) 185 - 194 2005.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Archives of Biochemistry and Biophysics
Activation of the phagocyte NADPH oxidase requires the regulatory proteins p47 phox and p67 phox , each harboring two SH3 domains. p67 phox interacts with p47 phox via simultaneous binding of the p67 phox C-terminal SH3 domain to both the proline-rich region (PRR) of amino acid residues 360-369 and its C-terminally flanking region of p47 phox ; the role of the interaction in oxidase regulation has not been fully understood. Here we show that the p47 phox -p67 phox interaction is disrupted not only by deletion of the PRR but also by substitution for basic residues in the extra-PRR (K383E/K385E). The substitution impaired oxidase activation partially in vitro and much more profoundly in vivo, indicating the significance of the p47 phox extra-PRR. Replacement of Ser-379 in the extra-PRR, a residue known to undergo phosphorylation in stimulated cells, by aspartate attenuates the interaction and thus results in a defective superoxide production, suggesting that phosphorylation of Ser-379 is involved in oxidase regulation. © 2005 Elsevier Inc. All rights reserved.
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Molecular composition and regulation of the Nox family NAD(P)H oxidases.
Sumimoto H, Miyano K, Takeya R
Biochemical and biophysical research communications 338 ( 1 ) 677 - 86 2005.12
Language：Japanese Publishing type：Research paper (scientific journal)
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PDIP38 associates with proteins constituting the mitochondrial DNA nucleoid.
Cheng X, Kanki T, Fukuoh A, Ohgaki K, Takeya R, Aoki Y, Hamasaki N, Kang D
Journal of biochemistry 138 ( 6 ) 673 - 8 2005.12
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The superoxide-producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells.
Kuroda J, Nakagawa K, Yamasaki T, Nakamura K, Takeya R, Kuribayashi F, Imajoh-Ohmi S, Igarashi K, Shibata Y, Sueishi K, Sumimoto H
Genes to cells : devoted to molecular & cellular mechanisms 10 ( 12 ) 1139 - 51 2005.12
Language：Japanese Publishing type：Research paper (scientific journal)
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Isoform-specific membrane targeting mechanism of Rac during Fc gamma R-mediated phagocytosis: positive charge-dependent and independent targeting mechanism of Rac to the phagosome.
Ueyama T, Eto M, Kami K, Tatsuno T, Kobayashi T, Shirai Y, Lennartz MR, Takeya R, Sumimoto H, Saito N
Journal of immunology (Baltimore, Md. : 1950) 175 ( 4 ) 2381 - 90 2005.8
Language：Japanese Publishing type：Research paper (scientific journal)
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Ueyama T., Eto M., Kami K., Tatsuno T., Kobayashi T., Shirai Y., Lennartz M., Takeya R., Sumimoto H., Saito N.
Journal of Immunology 175 ( 4 ) 2381 - 2390 2005.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Immunology
Rac1 and Rac2 are capable of stimulating superoxide production in vitro, but their targeting and functional mechanisms are still unknown. In the present study, we found that Rac1, 2, and 3 all accumulate at the phagosome during FcγR-mediated phagocytosis, and that the order of accumulation (Rac1 > Rac3 > Rac2) depends on the net positive charge in their polybasic (PB) regions (183-188 aa). Although all GFP-tagged prenylated PB regions of Rac isoforms (GFP-Rac(PB)) and GFP-tagged prenylated 6 Ala (GFP-6A) accumulated during phagocytosis, GFP-Rac2(PB) and GFP-6A showed weak accumulation at the phagosome through a linear structure connecting the phagosome and endomembranes. The PB region of Rac1 showed strong phospholipid interaction with PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P 3 , and phosphatidic acid, however, that of Rac1 did not. Constitutively active Rac2, GFP-Rac2(Q61L), was predominantly localized at the endomembranes; these endomembranes fused to the phagosome through the linear structure during phagocytosis, and this accumulation mechanism did not depend on positive charge in the PB region. Our conclusion is that Rac1 directly targets to the phagosome using the positively charged PB region and this accumulation mechanism is likely enhanced by the phospholipids. In addition to this mechanism, Rac2 has a positive charge-independent mechanism in which Rac2 initially targets to endomembranes and then these endomembranes fuse to the phagosome. Copyright © 2005 by The American Association of Immunologists, Inc.
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Fhos2, a novel formin-related actin-organizing protein, probably associates with the nestin intermediate filament.
Kanaya H, Takeya R, Takeuchi K, Watanabe N, Jing N, Sumimoto H
Genes to cells : devoted to molecular & cellular mechanisms 10 ( 7 ) 665 - 78 2005.7
Language：Japanese Publishing type：Research paper (scientific journal)
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The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators.
Ueno N, Takeya R, Miyano K, Kikuchi H, Sumimoto H
The Journal of biological chemistry 280 ( 24 ) 23328 - 39 2005.6
Language：Japanese Publishing type：Research paper (scientific journal)
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Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains.
Hirano Y, Yoshinaga S, Takeya R, Suzuki NN, Horiuchi M, Kohjima M, Sumimoto H, Inagaki F
The Journal of biological chemistry 280 ( 10 ) 9653 - 61 2005.3
Language：Japanese Publishing type：Research paper (scientific journal)
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Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells.
Kawahara T, Kohjima M, Kuwano Y, Mino H, Teshima-Kondo S, Takeya R, Tsunawaki S, Wada A, Sumimoto H, Rokutan K
American journal of physiology. Cell physiology 288 ( 2 ) C450 - 7 2005.2
Language：Japanese Publishing type：Research paper (scientific journal)
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On the mechanism of cell lysis by deformation.
Takamatsu H, Takeya R, Naito S, Sumimoto H
Journal of biomechanics 38 ( 1 ) 117 - 24 2005.1
Language：Japanese Publishing type：Research paper (scientific journal)
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Molecular mechanism underlying activation of superoxide-producing NADPH oxidases: roles for their regulatory proteins.
Sumimoto H, Ueno N, Yamasaki T, Taura M, Takeya R
Japanese journal of infectious diseases 57 ( 5 ) S24 - 5 2004.10
Language：Japanese Publishing type：Research paper (scientific journal)
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Sumimoto H., Ueno N., Yamasaki T., Taura M., Takeya R.
Japanese Journal of Infectious Diseases 57 ( 5 ) 2004.10
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Infectious Diseases
The phagocyte NADPH oxidase is dormant in resting cells but becomes activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defence. The catalytic core of this enzyme comprises the two membranous subunits gp91 phox /Nox2 and p22 phox . The oxidase activation requires the small GTPase Rae and the SH3 domain-containing proteins p47 phox and p67 phox , they normally exist in the cytoplasm and translocate upon cell stimulation to the membrane. The translocation depends on a stimulus-induced conformational change of p47 phox , which leads to the SH3 domain-mediated interaction with p22 phox , a binding required for the gp96 phox /Nox2-dependent super-oxide production. Activation of Nox1, an oxidase that is likely involved in host defence at the colon, requires novel proteins homologous to p47 phox and p67 phox , designated Noxo1 and Noxa1, respectively. Noxo1 and Noxa1, both expressed abundantly in the colon, are capable of constitutively activating Nox1. The constitutive activation may be due to the property of Noxo1: in contrast with p47 phox , Noxo1 seems to normally associate with p22 phox , which is required for the Nox1 activation. We will also describe the mechanism underlying regulation of the third oxidase Nox3, which exits in fetal kidney and inner ears.
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Identification of a novel type 1 diabetes susceptibility gene, T-bet.
Sasaki Y, Ihara K, Matsuura N, Kohno H, Nagafuchi S, Kuromaru R, Kusuhara K, Takeya R, Hoey T, Sumimoto H, Hara T
Human genetics 115 ( 3 ) 177 - 84 2004.8
Language：Japanese Publishing type：Research paper (scientific journal)
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Identification of a novel type 1 diabetes susceptibility gene, T-bet
Sasaki Y., Ihara K., Matsuura N., Kohno H., Nagafuchi S., Kuromaru R., Kusuhara K., Takeya R., Hoey T., Sumimoto H., Hara T.
Human Genetics 115 ( 3 ) 177 - 184 2004.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Human Genetics
The gene encoding interferon (IFN)-γ, IFNG, is known as one of the candidate susceptibility genes for type 1 diabetes. In addition, cytokines, including IFN-γ, play important roles in the pathogenesis of type 1 diabetes. Therefore, we focused on the Th1-specific T-box transcription factor gene (T-bet), which contributes to the induction of the hallmark Th1 cytokine, IFN-γ. We first screened for polymorphisms in the T-bet gene and detected two microsatellite repeat polymorphisms located in intron 1 and the 3′- flanking region, and two single nucleotide polymorphisms, including a His33Gln substitution within the coding region. By association studies, the Gln-positive phenotype and (CA) 14 allele in 3′-flanking region of T-bet were found to be associated with type 1 diabetes in the Japanese population. Furthermore, Gln33 T-bet showed a significantly higher transcriptional activity of the IFNG gene via a dual luciferase reporter assay. Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the T-bet gene, and that variation in T-bet transcriptional activity may play a role in the development of type 1 diabetes, possibly through the effect on IFN-γ production in Th1 cells. © Springer-Verlag 2004.
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Role of nicotinamide adenine dinucleotide phosphate oxidase 1 in oxidative burst response to Toll-like receptor 5 signaling in large intestinal epithelial cells.
Kawahara T, Kuwano Y, Teshima-Kondo S, Takeya R, Sumimoto H, Kishi K, Tsunawaki S, Hirayama T, Rokutan K
Journal of immunology (Baltimore, Md. : 1950) 172 ( 5 ) 3051 - 8 2004.3
Language：Japanese Publishing type：Research paper (scientific journal)
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Kawahara T., Kuwano Y., Teshima-Kondo S., Takeya R., Sumimoto H., Kishi K., Tsunawaki S., Hirayama T., Rokutan K.
Journal of Immunology 172 ( 5 ) 3051 - 3058 2004.3
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Immunology
The NADPH oxidase 1 (Nox1) is a gp91 phox homologue preferentially expressed in the colon. We have established primary cultures of guinea pig large intestinal epithelial cells giving 90% purity of surface mucous cells. These cells spontaneously released superoxide anion (O 2 - ) of 160 nmol/mg protein/h and expressed the Nox1, p22 phox , p67 phox , and Rac1 mRNAs, but not the gp91 phox , Nox4, p47 phox , p40 phox , and Rac2 mRNAs. They also expressed novel homologues of p47 phox and p67 phox (p41 nox and p51 nox , respectively). Human colon cancer cell lines (T84 and Caco2 cells) expressed the Nox1, p22 phox , p51 nox , and Rac1 mRNAs, but not the other NADPH component mRNAs, and secreted only small amounts of O 2 - ( < 2 nmol/mg protein/h). Cotransfection of p41 nox and p51 nox cDNAs in T84 cells enhanced PMA-stimulated O 2 - release 5-fold. Treatment of the transfected T84 cells with recombinant flagellin (rFliC) from Salmonella enteritidis further augmented the O 2 - release in association with the induction of Nox1 protein. The enhanced O 2 - production by cotransfection of p41 nox and p51 nox vectors further augmented the rFliC-stimulated IL-8 release from T84 cells. T84 cells expressed the Toll-like receptor 5, and rFliC rapidly phosphorylated TGF-β-activated kinase 1 and TGF-β-activated kinase 1-binding protein 1. A potent inhibitor for NF-κB (pyrrolidine dithiocarbamate) significantly blocked the rFliC-primed increase in O 2 - production and induction of Nox1 protein. These results suggest that p41 nox and p51 nox are involved in the Nox1 activation in surface mucous cells of the colon, and besides that, epithelial cells discern pathogenicities among bacteria to appropriately operate Nox1 for the host defense.
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Molecular mechanism for activation of superoxide-producing NADPH oxidases.
Takeya R, Sumimoto H
Molecules and cells 16 ( 3 ) 271 - 7 2003.12
Language：Japanese Publishing type：Research paper (scientific journal)
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Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation.
Takeya R, Sumimoto H
Journal of cell science 116 ( Pt 22 ) 4567 - 75 2003.11