Papers - TAKEYA Ryu
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The PB1 domain and the PC motif-containing region are structurally similar protein binding modules.
Yoshinaga S, Kohjima M, Ogura K, Yokochi M, Takeya R, Ito T, Sumimoto H, Inagaki F
The EMBO journal 22 ( 19 ) 4888 - 97 2003.10
Language：Japanese Publishing type：Research paper (scientific journal)
DOI： 10.1093/emboj/cdg475
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Takeya R., Ueno N., Kami K., Taura M., Kohjima M., Izaki T., Nunoi H., Sumimoto H.
Journal of Biological Chemistry 278 ( 27 ) 25234 - 25246 2003.7
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Biological Chemistry
The catalytic core of a superoxide-producing NADPH oxidase (Nox) in phagocytes is gp91 phox /Nox2, a membrane-integrated protein that forms a heterodimer with p22 phox to constitute flavocytochrome b 558 . The cytochrome becomes activated by interacting with the adaptor proteins p47 phox and p67 phox as well as the small GTPase Rac. Here we describe the cloning of human cDNAs for novel proteins homologous to p47 phox and p67 phox , designated p41 nox and p51 nox , respectively; the former is encoded by NOXO1 (Nox organizer 1), and the latter is encoded by NOXA1 (Nox activator 1). The novel homologue p41 nox interacts with p227 phox via the two tandem SH3 domains, as does p47 phox . The protein p51 nox as well as p67 phox can form a complex with p47 phox and with p41 nox 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 p47 phox and p67 phox activate the phagocyte oxidase via the same interactions. Indeed, p41 nox and p51 nox are capable of replacing the corresponding classical homologue in activation of gp91 phox . Nox1, a homologue of gp91 phox , also can be activated in cells, when it is coexpressed with p41 nox and p51 nox , with p41 nox and p67 phox , or with p47 phox and p51 nox ; 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 p41 nox and p51 nox likely function together or in combination with a classical one, thereby activating the two Nox family oxidases.
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Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation.
Ago T, Kuribayashi F, Hiroaki H, Takeya R, Ito T, Kohda D, Sumimoto H
Proceedings of the National Academy of Sciences of the United States of America 100 ( 8 ) 4474 - 9 2003.4
Language：Japanese Publishing type：Research paper (scientific journal)
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PAR3beta, a novel homologue of the cell polarity protein PAR3, localizes to tight junctions.
Kohjima M, Noda Y, Takeya R, Saito N, Takeuchi K, Sumimoto H
Biochemical and biophysical research communications 299 ( 4 ) 641 - 6 2002.12
Language：Japanese Publishing type：Research paper (scientific journal)
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PAR3β, a novel homologue of the cell polarity protein PAR3, localizes to tight junctions
Kohjima M., Noda Y., Takeya R., Saito N., Takeuchi K., Sumimoto H.
Biochemical and Biophysical Research Communications 299 ( 4 ) 641 - 646 2002.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications
The cell polarity protein PAR3, conserved from the nematode to the vertebrate, forms a complex with PAR6 and atypical protein kinase C (aPKC), and the protein complex occurs at the tight junctions in mammalian epithelial cells. Here we have cloned human cDNA for a novel PAR3 homologue, designated PAR3β, whose messages are present in a variety of tissues and most abundantly expressed in the adult and fetal kidneys. The encoded protein of 1205 amino acids contains a region homologous to the aPKC-binding domain of PAR3α, another human homologue previously identified, and three PDZ domains; the first PDZ domain of PAR3α is considered to interact with PAR6. Unexpectedly, in contrast to other PAR3s found in various species, PAR3β is incapable of binding to any isotypes of PAR6 or aPKC. Nevertheless PAR3β, expressed intrinsically or extrinsically, localizes to the tight junctions, indicating that the localization does not require the ternary complex formation. © 2002 Elsevier Science (USA). All rights reserved.
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Nox4, a novel homologue of the phagocyte NADPH oxidase catalytic subunit gp91<sup>phox</sup>
Shiose A., Kuribayashi F., Takeya R., Sumimoto H.
International Congress Series 1233 ( C ) 63 - 68 2002.11
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Congress Series
During phagocytosis, the NADPH oxidase in neutrophils produces superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. The phagocyte oxidase contains the two subunits p22 phox and gp91 phox , the latter of which contains binding sites for the heme, FAD, and NADPH, forming the complete electron-transporting apparatus. Recent studies have revealed that four nonphagocytic homologues of gp91 phox exist, including Nox4, whose cDNA we have currently cloned. Here we describe the molecular nature of Nox4, in comparison with those of other members of the NAD(P)H oxidase family. © 2002 Elsevier Science B.V.
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Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67(phox), Grb2 and Pex13p.
Kami K, Takeya R, Sumimoto H, Kohda D
The EMBO journal 21 ( 16 ) 4268 - 76 2002.8
Language：Japanese Publishing type：Research paper (scientific journal)
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Kami K., Takeya R., Sumimoto H., Kohda D.
EMBO Journal 21 ( 16 ) 4268 - 4276 2002.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：EMBO Journal
The basic function of the Src homology 3 (SH3) domain is considered to be binding to proline-rich sequences containing a PxxP motif. Recently, many SH3 domains, including those from Grb2 and Pex13p, were reported to bind sequences lacking a PxxP motif. We report here that the 22 residue peptide lacking a PxxP motif, derived from p47 phox , binds to the C-terminal SH3 domain from p67 phox . We applied the NMR cross-saturation method to locate the interaction sites for the non-PxxP peptides on their cognate SH3 domains from p67 phox , Grb2 and Pex13p. The binding site of the Grb2 SH3 partially overlapped the conventional PxxP-binding site, whereas those of p67 phox and Pex13p SH3s are located in different surface regions. The non-PxxP peptide from p47 phox binds to the p67 phox SH3 more tightly when it extends to the N-terminus to include a typical PxxP motif, which enabled the structure determination of the complex, to reveal that the non-PxxP peptide segment interacted with the p67 phox SH3 in a compact helix-turn-helix structure (PDB entry 1K4U).
DOI： 10.1093/emboj/cdf428
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Nox4, a novel homologue of the phagocyte NADPH oxidase catalytic subunit gp91phox
Shiose A, Kuribayashi F, Takeya R, Sumimoto H
Int. Congr. Ser 1233 63 - 68 2002
Language：English Publishing type：Research paper (scientific journal)
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The PX domain as a novel phosphoinositide-binding module
Ago T., Takeya R., Hiroaki H., Kuribayashi F., Ito T., Kohda D., Sumimoto H.
Biochemical and Biophysical Research Communications 287 ( 3 ) 733 - 738 2001.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications
The phox (phagocyte oxidase) homology (PX) domain occurs in the mammalian phox proteins p40 phox and p47 phox , the polarity establishment protein Bem1p in budding yeast, and a variety of proteins involved in membrane trafficking. Here we show that the PX domains of p40 phox and p47 phox directly bind to phosphoinositides: p40 phox prefers Ptdlns(3)P, while p47 phox does Ptdlns(4)P and Ptdlns(3,4)P 2 . In addition, the Bem1p PX domain also interacts with Ptdlns(4)P. When the p40 phox PX domain is expressed as a fusion to green fluorescent protein in HeLa cells, it exists at early endosomes where Ptdlns(3)P is enriched. Furthermore, a mutant p40 phox PX carrying the substitution of Lys for Arg105 only weakly binds to phosphoinositides in vitro, and fails to locate to early endosomes. Thus the PX domain functions as a novel phosphoinositide-binding module and likely participates in targeting of proteins to membranes. © 2001 Academic Press.
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Noda Y., Takeya R., Ohno S., Naito S., Ito T., Sumimoto H.
Genes to Cells 6 ( 2 ) 107 - 119 2001.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Genes to Cells
Background: Asymmetric cell division in the Caenorhabditis elegans embryos requires products of par (partitioning defective) genes 1-6 and atypical protein kinase C (aPKC), whereas Cdc42 and Rac, members of the Rho family GTPases, play an essential role in cell polarity establishment in yeast and mammalian cells. However, little is known about a link between PAR proteins and the GTPases in cell polarization. Results: Here we have cloned cDNAs for three human homologues of PAR6, designated PAR6α, β and γ, comprising 345, 372 and 376 amino acids, respectively. The PAR6 proteins harbour a PDZ domain and a CRIB-like motif, and directly interact with GTP-bound Rac and Cdc42 via this motif and with the aPKC isoforms PKCι/λ and PKCζ via the N-terminal head-to-head association. These interactions are not mutually exclusive, thereby allowing the PAR6 proteins to form a ternary complex with the GTPases and aPKC, both in vitro and in vivo. When PAR6 and aPKC are expressed with a constitutively active form of Rac in HeLa or COS-7 cells, these proteins co-localize to membrane ruffles, which are known to occur at the leading edge of polarized cells during cell movement. Conclusion: Human PAR6 homologues most likely play an important role in the cell polarization of mammalian cells, by functioning as an adaptor protein that links activated Rac and Cdc42 to aPKC signalling.
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The PX domain as a novel phosphoinositide- binding module.
Ago T, Takeya R, Hiroaki H, Kuribayashi F, Ito T, Kohda D, and Sumimoto H
Biochem. Biophys. Res. Commun. 287 733 - 738 2001
Language：English Publishing type：Research paper (scientific journal)
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Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C.
Noda Y, Takeya R, Ohno S, Naito S, Ito T, and Sumimoto H
Genes Cells 6 107 - 119 2001
Language：English Publishing type：Research paper (scientific journal)
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A novel intracellular membrane-bound calcium-independent phospholipase A<inf>2</inf>
Tanaka H., Takeya R., Sumimoto H.
Biochemical and Biophysical Research Communications 272 ( 2 ) 320 - 326 2000.6
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications
We have cloned human cDNA encoding a novel protein of 782 amino acids that contains the lipase consensus sequence Gly-Xaa-Ser-Xaa-Gly and several stretches surrounding the motif, which are homologous to those of the catalytic domain of cytosolic calcium-independent phospholipase A 2 (iPLA 2 ). When expressed in COS-7 cells, the protein predominantly exists in the membrane fraction and exhibits a phospholipase A 2 activity in a calcium-independent manner. The transcript of the membrane-bound iPLA 2 gene is ubiquitously observed as a single band of approximately 3.3 kb on Northern blot, with the most abundant expression in the skeletal muscle and heart. By a search of the database, we have also identified its putative C. elegans homologue, which shows 47% identity with that of human in the iPLA 2 catalytic region. Thus the novel type of iPLA 2 is evolutionarily well conserved, suggestive of its biological significance. (C) 2000 Academic Press.
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Interaction of the PDZ domain of human PICK1 with class I ADP-ribosylation factors
Takeya R., Takeshige K., Sumimoto H.
Biochemical and Biophysical Research Communications 267 ( 1 ) 149 - 155 2000.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications
We have cloned the cDNA encoding human PICK1 (protein interacting with C kinase 1), a PDZ domain-containing protein of 415 amino acids, and also identified the Drosophila homologue by search of the databank. Northern blot analysis shows a single mRNA of about 2.0 kb ubiquitously expressed in human tissues. Although PICK1 proteins harbor a region homologous to arfaptin1 and arfaptin2, two proteins that bind to the ARF (ADP-ribosylation factor), this region of PICK1 does not interact with ARFs in the yeast two-hybrid system. On the other hand, the PDZ domain of PICK1 is capable of interacting with constitutively active, GTP-bound forms of ARF1 and ARF3, but neither with those of ARF5/6 nor with the GDP-bound ARFs. The PICK1-ARF interaction is abrogated by introduction of mutations in the PDZ domain or by deletion of the extreme C-terminus of ARF1. Thus, PICK1 specifically interacts with ARF1/3 in the GTP-bound state, suggesting that PICK1 participates in ARF1/3-mediated cellular processes. (C) 2000 Academic Press.
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A novel intracellular membrane-bound calcium-independent phospholipase A2.
Tanaka H., Takeya R, Sumimoto H
Biochem. Biophys. Res. Commun. 272 320 - 326 2000
Language：English Publishing type：Research paper (scientific journal)
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Interaction of the PDZ domain of human PICK1 with class I ADP-ribosylation factors.
Takeya R, Takeshige K, Sumimoto H
Biochem. Biophys. Res. Commun. 267 149 - 155 2000
Language：English Publishing type：Research paper (scientific journal)
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Izuhara K., Arinobu Y., Sumimoto H., Nunoi H., Takeya R., Higuchi K., Takeshige K., Hamasaki N., Harada N.
Molecular Immunology 36 ( 1 ) 45 - 52 1999.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Molecular Immunology
Interleukin (IL)-4 plays an important role in IgE synthesis in B cells and in Th2 differentiation in T cells, IL-4 conducts its biological activities through binding to the IL-4 receptor (IL-4R) on the surface of target cells. IL-4R are thought to be composed of the IL-4R α chain (IL- 4Rα) and either the IL-2R γ chain or the IL-13R α chain. We have previously shown that the membrane-proximal portion in the cytoplasmic domain of the human IL-4Rα (hIL-4Rα) is critical for proliferation, generation of germline ε transcript, and activation of STAT6, based on analyses of truncated hIL-4Rαs. In this study, we found that p47p(phox), an activator of the phagocyte NADPH oxidase, binds to this portion by the two-hybrid system. Furthermore, we observed the association of p47(phox) with the hIL-4Rα in B cells derived from a normal donor. These results suggest that p47(phox) is involved in the signal transduction of IL-4 in B cells. However, activation of STAT6, CD23 expression, and IgE synthesis induced by IL-4 were not affected in p47(phox)-deficient patients, which raises the possibility that p47(phox) may be important in other signaling activities as well in B cells.
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Association of the interleukin-4 receptor a chain with p47phox, an activator of the phagocyte NADPH oxidase in B cells.
Izuhara K*, Arinobu Y, Sumimoto H, Nunoi H, Takeya R, Higuchi K, Takeshige K, Hamasaki N, Harada N.
Mol. Immunol. 36 45 - 52 1999
Language：English Publishing type：Research paper (scientific journal)