獲得性生体情報の構築・応答ならびにその異常と病態の研究

• Project/Area Number: 12CE2006
• Research Category: Grant-in-Aid for COE Research
• Allocation Type: Single-year Grants
• Research Institution: Kyoto University
• Principal Investigator: 本庶 佑 京都大学, 医学研究科, 教授 (80090504)
• Co-Investigator(Kenkyū-buntansha): 中西 重忠 京都大学, 生命科学研究科, 教授 (20089105) ; 湊 長博 京都大学, 生命科学研究科, 教授 (40137716) ; 北 徹 京都大学, 医学研究科, 教授 (60161460)
• Project Period (FY): 2000 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥2,280,000,000 (Direct Cost: ¥1,950,000,000、Indirect Cost: ¥330,000,000); Fiscal Year 2004: ¥468,000,000 (Direct Cost: ¥360,000,000、Indirect Cost: ¥108,000,000); Fiscal Year 2003: ¥468,000,000 (Direct Cost: ¥360,000,000、Indirect Cost: ¥108,000,000); Fiscal Year 2002: ¥494,000,000 (Direct Cost: ¥380,000,000、Indirect Cost: ¥114,000,000); Fiscal Year 2001: ¥470,000,000 (Direct Cost: ¥470,000,000); Fiscal Year 2000: ¥380,000,000 (Direct Cost: ¥380,000,000)
• Keywords: クラススイッチ / 体細胞突然変異 / AID / PD-1 / PD-L / IMCT法 / LDL受容体 / グルタミン酸受容体 / SPA-1 / パーキンソン / 立体構造

Research Abstract

本庶グループは、AIDの突然変異体を用いてAIDのN末端が体細胞突然変異に、C末端がクラススイッチ組換えに必要な機能特異的ドメインであることを証明した。一方、DNA deamination学説において、中心的な役割をすると考えられているウラシルDNAグリコシラーゼ(UNG)がDNAの切断には関与せず、この酵素の役割は酵素活性を通じてではなく、そのタンパク質として関与することを明かにした。一方、PD-1の自己免疫制御についてはPD-1欠失が自己免疫性糖尿病の発症を著しく促進し、この実験系を用いてNODマウスの糖尿病感受性遺伝子座の解析が可能であることを示した。
湊グループは、SPA-1 KOマウスの新しい病態形質として、抗DNA抗体・抗核抗体の産生とそれによる典型的なループス腎炎の発症を確認した。これは異常な自己反応性B1細胞の出現とその抗原特異的免役応答によるもので、構成的Rap1シグナルによる転写共因子OcaBの過剰発現による免疫グロブリンL鎖の編集(レセプター・エディション)異常に起因することが示された。レセプター・エディションの異常による自己免疫病の発症は従来、自己抗体遺伝子トランスジェニック・モデルを用いて精力的に研究が進められてきたが、今回の結果により、通常の動物のシグナル遺伝子変異によるレセプター・エディションの異常が確かにヒトのループスに相当する自己免疫病態に至りうることが示された。
中西グループは、グルタミン酸受容体と共役するイオン・チャンネル及び新たな足場蛋白質(GIRK・K+チャンネル、ubiquitin ligase、tamalin等)を明らかにし、これらの複合体形成がグルタミン酸伝達の制御に重要な役割を果たしていることを示した。さらに小脳発達期の顆粒細胞の増殖、移動、分化、シナプス形成にカルシニュリン・シグナル系が重要な役割を果たし、BDNFとCa2+シグナルの協調的作用がグルタミン酸系シナプス成熟に必須であることを示した。また、大脳皮質の構築を制御するCaja1-Retzius(CR)細胞の特異的遺伝子を同定し、CR細胞が細胞増殖、分化、シナプス成熟に特異性を持って作用していることを示した。
北グループは、彼らが同定した酸化LDL受容体LOX-1の血清濃度が急性冠症候群で上昇しており血清LOX-1値は急性冠症侯群の予知因子となる可能性を示した。北らが同定した別の酸化LDL受容体SR-PSOX(CXCL16と同一)は感染性心内膜炎等で心臓の弁内皮細胞に強発現しCD8T細胞のVCAM-1への接着を促進し、IFNγの産生を増加さることを発見した。GFP発現マウスの骨髄移植マウスで実験的動脈硬化を解析し血管平滑筋様細胞も含めて浸潤した多くの細胞が骨髄由来であることを見出した。アダプター蛋白ShcAがインテグリンβ3のチロシンリン酸化依存的に結合し、血小板凝集に重要であることを証明した。

Research Products

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• [Publications] Abe M: "GATA-6 is involved in PPARgamma-mediated activation of differentiated phenotype in human vascular smooth muscle cells."Arterioscler Thromb Vasc Biol.. 23. 404-410 (2003)
• [Publications] Yanazume T: "Cardiac p300 is involved in myocyte growth with decompensated heart failure."Mol Cell Biol.. 23. 3593-3606 (2003)
• [Publications] Watanabe T.: "Helper CD4+T cells for IgE response to a dietary antigen develop in the liver."J Allergy Clin Immunol.. 111. 1375-1385 (2003)
• [Publications] Shimaoka T: "Cutting edge : SR-PSOX/CXC chemokine ligand 16 mediates bacterial phagocytosis by APCs through its chemokine domain."J Immunol. 171. 1647-1651 (2003)
• [Publications] Itoh T.: "A coordinated cytotoxic effect of IFN-gamma and cross-reactive antibodies in the pathogenesis of Helicobacter pylori gastritis."Helicobacter.. 8. 268-278 (2003)
• [Publications] Izumi T.: "Reinduction of T-type calcium channels by endothelin-1 in failing hearts in vivo and in adult rat ventricular myocytes in vitro."Circulation.. 108. 2530-2535 (2003)
• [Publications] Handa T.: "Glomerulonephritis induced by methicillin-sensitive Staphylococcus aureus infection"Clin Exp Nephrol.. 7. 247-249 (2003)
• [Publications] Yamada SI: "Small conductance Ca2+-dependent K+ channels are the target of spike-induced Ca2+ release in a feedback regulation of pyramidal cell excitability."J Neurophysiol.10.1152/jn.01049.2003.. Dec.24. (2003)
• [Publications] Yamauchi R: "Upregulation of SR-PSOX/CXCL16 and recruitment of CD8+T cells in cardiac valves during inflammatory valvular heart disease."Arterioscler Thromb Vasc Biol.. 24. 282-287 (2004)
• [Publications] Shirakawa R: "Munc13-4 is a GTP-Rab27 binding protein regulating dense-core granule secretion in platelets."J Biol Chem.. 279. 10730-10737 (2004)
• [Publications] Xu Y: "Role of Bone Marrow-Derived Progenitor Cells in Cuff-Induced Vascular Injury in Mice."Arterioscler Thromb Vasc Biol.. 24. 477-484 (2004)
• [Publications] Shimaoka T: "Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells."J Leukoc Biol.. 75. 267-274 (2004)
• [Publications] Bross, L: "DNA double-strand breaks : Prior to but not sufficient in targeting hypermutation"J. Exp. Med.. 195. 1187-1192 (2002)
• [Publications] Yoshikawa, K.: "The AID enzyme induces hypermutation in an actively transcribed gene in fibroblasts"Science. 296. 2033-2036 (2002)
• [Publications] Watanabe, N: "Activation and differentiation of autoreactive B-1 cells by interleukin 10 induce autoimmune hemolytic anemia in Fas-deficient anti-erythrocyte immunoglobulin transgenic mice"J. Exp. Med.. 196. 141-146 (2002)
• [Publications] Honjo, T.: "Does AID need anther aid?"Nature Immunol.. 3. 800-801 (2002)
• [Publications] Iwai, Y.: "Microanatomical localization of PD-1 in human tonsils"Immunology Letters. 83. 215-220 (2002)
• [Publications] Ishida, M.: "Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues"Immunology Letters. 84. 57-62 (2002)
• [Publications] Iwai, Y.: "Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade"Proc. Natl. Acad. Sci. USA. 99. 12293-12297 (2002)
• [Publications] Okazaki, T.: "New regulatory co-receptors : inducible co-stimulator and PD-1"Curr. Opin. Immunol.. 14. 779-782 (2002)
• [Publications] Fagarasan, S.: "Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora"Science. 298. 1424-1425 (2002)
• [Publications] Fagarasan, S.: "Intestinal IgA synthesis : regulation of front-line body defences"Nature Rev. Immunol.. 3. 63-72 (2003)
• [Publications] Yamamoto, N.: "Notch/RBP-J signaling regulates the epidermis/hair fate determination of hair follicular stem cells"Current Biology. 13. 333-338 (2003)
• [Publications] Kuroda, K.: "Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway"Immunity. 18. 301-312 (2003)
• [Publications] Doi, T.: "De novo protein synthesis is required for the activation-induced cytidine deaminase function in class-switch recombination"Natl. Acad. Sci. USA. 100. 2634-2638 (2003)
• [Publications] Tanigaki, K: "Regulation of B cell development by Notch/RBP-J signaling"Immunol.. (in press). (2003)
• [Publications] Watanabe, N: "Elimination of local macrophages in the intestine prevents chronic colitis in interleukin-10 deficient mice"Digestive Diseases and Science2002. (in press). (2003)
• [Publications] Schroeder, T.: "Recombination signal sequence binding protein Jk alters mesodermal cell fate decisions by suppressing cardiomyogenesis"Proc. Natl. Acad. Sci. USA. (in press). (2003)
• [Publications] Hatachi, S.: "CD4+PD-1+ T cells accumulate as unique anergic cells in synovial fluid from rheumatoid arthritis patients"Journal of Rheumatology. (in press). (2003)
• [Publications] Kitano, J.: "Tamalin, a PDZ Domain-containing protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins"J. Neurosci.. 22. 1280-1289 (2002)
• [Publications] Renger, J.J.: "Experience-dependent plasticity without long-term depressionvia mGluR2 in developing visual cortex"Proc. Natl. Acad. Sci. USA. 99. 1280-1289 (2002)
• [Publications] Hazama, M.: "Different regulatory sequences are required for parvalbumin gene expression in skeletal muscles and neuronal cells of transgenic mice"Mol. Brain. Res.. 100. 53-66 (2002)
• [Publications] Higashida, H.: "Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells"J. Neurochem.. (in press). (2003)
• [Publications] Sato. T.: "Amino acid mutagenesis of the ligand binding site and the dimer interface of the metabotropic glutamate receptor 1"J. Biol. Chem.. (in press). (2003)
• [Publications] Kitano, J.: "Tamalin is a scaffold protein that interacts with multiple neuronal proteins in distinct modes of protein-protein association"J. Biol. Chem.. (in press). (2003)
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• [Publications] Katagiri, K: "Rap1 functions as a key regulator of T cell and APC interactions and modulates T cell-responses"Mol. Cell. Biol.. 22. 1001-1015 (2002)
• [Publications] Ishida, M.: "Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues"Immunol. Letters. 84. 57 (2002)
• [Publications] Iwai, Y.: "Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade"Proc. Natl. Acd. Sci. USA. 99. 12293-12297 (2002)
• [Publications] Kato, Y.: "Requirement of species-specific cognate interactions for the activation of human γδ T cells by pamidronate"J. Immunol.. (in press). (2003)
• [Publications] Su, L.: "AF-6 negatively regulates integrin-mediated cell adhesion by binding both Rap1 GTP and Rap1 GTPase-activating proteins and enhancing Rap1 inactivation"J. Biol. Chem.. (in press). (2003)
• [Publications] Yamanaka, K.: "Identification of the ubiquitin-protein ligase that recognizes hemeoxidized IRP2"Nature Cell Biol.. (in press). (2003)
• [Publications] T.Wada: "Health Status And Subjective Economic Papua"Lancet. 360. 51 (2002)
• [Publications] M.Matsuzaki: "Large Scale Cohort Study of the Relationship Between Serum Cholesterol Concentration and Coronary Events With Low-Dose Simvastatin Therapy in Japanese Patients With Hypercholesterolemia. -Primary Prevention Cohort Study of the Japan Lipid Intervention Trial(J-LIT)"Circulation J.. 66. 1087-1095 (2002)
• [Publications] Fukuhara, A: "Involvement of Nectin in the Localization of Junctional of Adhesion Molecule at Tight Junctions"Oncogene. 21. 7642-7655 (2002)
• [Publications] Morimoto, M.: "A mouse model of cerebral aneurysm-experimental induction by renal hypertesion and local hemodynamic changes"Stroke. 33・7. 1911-1915 (2002)
• [Publications] Tanaka, M.: "Regional cerebral blood flow abnormalities in non-demented patients with memory impairment"J. Neuroimaging. 12・2. 112-118 (2002)
• [Publications] Sano, H.: "Blockade of Platelet-Derived Growth Factor Receptor-β Pathway Induces Apoptosis of Vascular Endothelial Cells and Disrupts Glomerular Capillary Formation in Neonatal Mice"Am. J. Pathol.. 161. 135-143 (2002)
• [Publications] Yanagita, M.: "Essential role of Gas6 for glomerular injury in nephrotoxic nephritis"J. Clin. Invest.. 110. (2002)
• [Publications] Ho, H.K.: "Hypertension in Japanese old-old"Lancet. 359. 804 (2002)
• [Publications] Hayashida, K.: "Lectin-like oxidized LDL receptor-1 (LOX-1) supports adhesion of mononuclear leukocytes and a monocyte-like cell line THP-1 cells under static and flow conditions"FEBS Lett.. 511. 170-174 (2002)
• [Publications] Watanabe, T.: "Administration of an antigen at a high dose generates regulatory CD4+ T cells expressing CD95 ligand and secreting IL-4 in the liverl"J Immunol.. 168. 2188-2199 (2002)
• [Publications] Ashida N.: "Vortex-mediated mechanical stress induces integrin-dependent cell adhesion mediated by inositol-1,4,5 triphosphate-sensitive Ca2+ release in THP-1 cells"J Biol Chem. 278. 9327-9331 (2003)
• [Publications] Kataoka, K.: "LOX-1 Pathway affects the extent of myocardial ischemia-reperfusion injury. Biochem. and Biophys."Res. Commun.. 300. 656-660 (2003)
• [Publications] Tanigaki, K.: "Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate"Neuron. 29. 45-55 (2001)
• [Publications] Latchman, Y.: "PD-L2, a novel B7 homologue, is a second ligand for PD-1 and inhibits Tcell activation"Nature Immunol.. 2. 261-268 (2001)
• [Publications] Nishimura, H.: "Autoimmune dilated cardiomyopathy in PD-i receptor deficient mice"Science. 291. 319-322 (2001)
• [Publications] Tani, S.: "The amino-and carboxy-terminal regions of RBP-J interact with the ankyrin repeats of Notch1 RAMIC to activate transcription"Nucleic Acids Res.. 29. 1373-1380 (2001)
• [Publications] Muramatsu, M.: "Complex layers of genetic alteration in generation of antibody diversity"Trends in Immunol.. 22. 66-68 (2001)
• [Publications] Tashiro, J.: "Palindromic but not G-rich sequences are targets of class switch recombination"Int. Immunol.. 13. 495-505 (2001)
• [Publications] Okazaki, T.: "The regulation ofPD-1/PD-L1 pathway and autommune diseases"Activating and Inhibitory Immunoglobulin-like Receptors. 211-214 (2001)
• [Publications] Agata, Y.: "Histone acetylation determines the developmentally regulated accessibility for TCRγ gene recombination"J.Exp.Med.. 193. 873-879 (2001)
• [Publications] Nishimura, H.: "PD-1:an inhibitory immunoreceptor involved in peripheral tolerance"Trend Immunol.. 22. 265-268 (2001)
• [Publications] Ikegawa, M.: "Elevated plasma stromal cell-derived factor 1 protein level in the progression of HIV type 1 infection/AIDS"Aids Res Hum Retroviruses. 17. 587-595 (2001)
• [Publications] Kinoshita, K.: "Linking class-switch recombination with somatic hypermutation"Nature Reviews MCB. 2. 493-503 (2001)
• [Publications] Lee, H.: "Induction of germline transcription in the human T cell receptor γ locus by STAT5"J. Immunol.. 167. 320-326 (2001)
• [Publications] Ye, S-K.: "Differential roles of cytokine receptors in the developmentof epidermal γδ T cells^1"J. Immunol.. 167. 1929-1934 (2001)
• [Publications] Mizutani, T.: "Conservation of the biochemical mechanisms of signal transduction among mammalian Notch family members"Proc. Nati. Acad. Sci. USA. 98. 9026-9031 (2001)
• [Publications] Lee, C-G.: "Quantitative regulation of class switch Yoshida M recombination by S region transcription"J.Exp. Med.. 194. 365-373 (2001)
• [Publications] Durandy, A.: "Human genetic defects in class-switch recombination (hyper-IgM syndromes)"Curr.Opin.Immunol.. 13. 543-548 (2001)
• [Publications] Kobuke, K.: "ESDN, a Novel neuropiin-like membrane protein cloned from vascular cells with the longest secretory signal sequence among eukaryotes, is upregulated after vascular injury"J. Biol. Chem.. 276. 34105-34114 (2001)
• [Publications] Fagarasan, S.: "In situ class switching and differentiation to IgA-producing cells in the gut lamina propria"Nature. 413. 639-643 (2001)
• [Publications] Kinoshita, K.: "A hallmark of active class switch recombination: transcripts directed by I promoters on looped-out circular DNAs"Proc. Natl. Acad. Sci. USA. 98. 12620-12623 (2001)
• [Publications] Okazaki, T.: "PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine"Proc. Natl. Acad. Sci. USA. 98. 13866-13871 (2001)
• [Publications] Chen, X.: "Variable deletion and duplication at recombination junction ends: implication for staggered double-strand cleavage in class switch recombination"Proc. Natl. Acad. Sci. USA. 98. 13860-13865 (2001)
• [Publications] Ye, S-K.: "The IL-7 receptor controls the accessibility of the TCRγ locus by stat5 and histone acetylation"Immunity. 15. 813-823 (2001)
• [Publications] Petersen, S.: "AID is required to initiate Nbs 1/γ-H2AX focus formation and mutations at sites of class switching"Nature. 414. 660-665 (2001)
• [Publications] Higuchi, T.: "Cutting Edge: Ectopic expression of CD40 ligand on B cells induces lupus-like autoimmune disease 1"J. Immunol. 168. 9-12 (2002)
• [Publications] Shinohara, M.: "Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice"Proc. Nati. Acad. Sci. USA. 99. 1383-1388 (2002)
• [Publications] Honjo, T.: "Molecular mechanism of class switch recombination: linkage with somatic hypermutation"Ann. Rev. Immunol.. 20. 165-196 (2002)
• [Publications] Nagaoka, H.: "MD-directed hypermutation in the immunoglobulin Sμ region: Implication to AID involvement in a common step of class switch recombination and somatic hypermutation"J. Exp. Med.. 195. 529-534 (2002)
• [Publications] Nakamura, T.: "Fibulin-5/DANCE is essential for elastogenesis in vivo"Nature. 415. 171-175 (2002)
• [Publications] Okazaki, I.: "AID induces class switch recombination in fibroblasts"Nature (DOI 10.1038/nature 727). (in press). (2002)
• [Publications] Fagarasan, S.: "Experimental models of autoimmune hemolytic anemia"The Molecular Pathology of Autoimmmune Diseases, Second edition, Gordon and Breach/Harwood. (in press). (2002)
• [Publications] Krnoshita, K.: "Switch region"Encyclopedia of Melecular Medicine. (in press). (2002)
• [Publications] Bross, L.: "DNA double-strand breaks: Prior to but not sufficient in targeting hypermutation"J.Exp.Med.. (in press). (2002)
• [Publications] Taniguchi, Y.: "Notch receptor cleavage is dependent on but not directly executed by presenilins"Proc. Nati. Acad. Sci. USA. (in press). (2002)
• [Publications] Han, H.: "Inducible gene knockout of transcription factor RBP-J reveals its essential role in T versus B lineage decision"Int. Immunol.. (in press). (2002)
• [Publications] Yoshida, K.: "A key role of starburst amacrine cells in originating retinal directional selectivity and optokinetic eye movement"Neuron. 30. 771-780 (2001)
• [Publications] Sato, M.: "NMDA receptor stimulation and brain-derived neurotrophic factor upregulate Homer 1a mRNA via the mitogen-activated protein kinase cascade in cultured cerebellar granule cells"J. Neurosci.. 21. 3797-3805 (2001)
• [Publications] Shinohara Y.: "Glutamate induces focal adhesion kinase tyrosine phosphorylation and actin rearrengement in heterologous mGluRl-expressing CHO cells via calcium/calmodulin signalin"J. Neurochem.. 78. 365-373 (2001)
• [Publications] Hikida, T.: "Increased sensitivity to cocaine by cholinergic cell ablation in nucleus accumbens"Proc. Nati. Acad. Sci. USA. 98. 13351-13354 (2001)
• [Publications] Dev, K. K.: "Regulation of mglu(7) receptors by proteins that interact with the intracellular C-terminus"Trends Pharmacological Sciences. 22(7). 355-361 (2001)
• [Publications] Kitano, J.: "Tamalin, a PDZ domain-containing protein links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins"J.Neurosci.. (in press). (2002)
• [Publications] John J. R.: "Experience-dependent plasticity without long-term depression by means of type 2 metabotropic glutamate receptors in developing visual cortex"Proc. Natl. Acad. Sci. USA. (in press). (2002)
• [Publications] Suga.K.: "CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation"FEBS Letters. 489. 249-253 (2001)
• [Publications] Nishimura, H.: "Autoimmune dilated cardiomyopathy in PD-1 reptor deficient mice"Science. 291. 319-322 (2001)
• [Publications] Miyagawa, F.: "Essential requirement of antigen presentation by monocyte-lineage cells for the activation of primary human gd T cells by aminobisphosphonate antigen"J.Immunol. 166. 166. 5508-5514 (2001)
• [Publications] Kawakami, T.: "NEDD8 recruits E2-ubiquitin to SCE E3 ligase"EMBO J.. 20. 4003-4012 (2001)
• [Publications] Kato, Y.: "Targeting of tumor cells for human gamma delta T cells by nonpeptide antigens"J. Immunol. 167. 5092-5098 (2001)
• [Publications] Miyagawa, F.: "Essential contribution of germilne-encoded residues in Jg1.2 segment to the recognition of nonpeptide antigens by human gd T cells"J. Immunol. 167. 6773-6779 (2001)
• [Publications] Okuda H: "The Von Hippel-Lindau (VHL) tumor suppressor protein mediates ubiquitination of activated atypical protein krnase C"J Biol Chem.. 276. 43611-4361 (2001)
• [Publications] Katagiri, K.: "Rap 1 functions as a key regulator of T cell and APC interactions and modulates T cell-responses"Mol. Cell. Biol.. 22. 1001-1015 (2002)
• [Publications] Suganuma M: "Helicobacter pylon membrane protein 1: a new carcinogenic factor of Helicobacter pylori"Cancer Res.. 61. 6356-6359 (2001)
• [Publications] Yoshida M: "CD4 T cells monospecific to ovalbumin produced by Eschelichia coil can induce colitis upon transfer to BALB/c and SCID mice"Int. Immunology. 13. 1561-1570 (2001)
• [Publications] Watanabe T: "Oral administration of an antigen at a high dose generates tolerogenicCD4+CD25+ T cells expressing CD95 ligand in the liver"J. Immunol:. 168. 2188-2199 (2001)
• [Publications] Hayashida K: "Lectin-like oxidized LDL receptor-i (LOX-1) supports adhesion of mononuclearleukocytes and a monocyte-like cell line THP-1 cells under static and flow conditions"FEBS Lett.. 511. 170-174 (2001)
• [Publications] Hashimoto K: "Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse ostnatal cerebellar development"J. Neurosci.. 21. 9701-9712 (2001)
• [Publications] Onoe H: "Cortical networks recruited for time perception: A monkey positron emission tomography (PET) study"Neuroimage. 13. 37-45 (2001)
• [Publications] Nishioka H: "Small GTPase Rho regulates thrombin-induced platelet aggregation. Biochem"Biophys. Res. Commun. 280. 970-975 (2001)
• [Publications] Sano H: "Functional blockade of platelet-derived growth factor receptor-b but not ofreceptor-a prevents vascular smooth muscle cell accumulation in the fibrouscap lesions in apoliporotein E-deficient mice"Circulation. 103. 2955-2960 (2001)
• [Publications] Nishioka H: "Small GTPase Rho regulates thrombin-induced platelet aggregation. Biochem"Biophys. Res. Commun. 280. 970-975 (2001)
• [Publications] Onoe H: "Cortical networks recruited for time perception: A monkey positron emission tomography (PET) study"Neurolmage. 13. 37-45 (2001)
• [Publications] Hashimoto K: "Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse eliminationdurin postnatal cerebellar develop meat"J. Neurosci.. 21. 9701-9712 (2001)
• [Publications] Hayashida K.: "Lectin-like oxidized LDL receptor-i (LOX-1) supports adhesion of mononuclear leukocytes and a monocyte-like cell line THP-1 cells under static and flow conditions"FEBS Lett.. 511. 170-174 (2001)
• [Publications] Watanabe T: "Oral administration of an antigen at a high dose generates tolerogenicCD4+CD25+ T cells expressing CD95 ligand in the liver"J. Immunol.. 168. 2188-2199 (2001)
• [Publications] Yoshida M: "CD4 T cells monospecific to ovalbumin produced by Eschelichia coli can induce colitis upon transfer to BALB/c and SCID mice"Int. Immunology. 13. 1561-1570 (2001)
• [Publications] Suganuma M: "Helicobacter pylori membrane protein 1: a new carcinogernc factor of Helicobacter pylori"Cancer Res.. 61. 6356-6359 (2001)
• [Publications] Latchman,Y.,(中略)Nishimura,H.,Honji,T.,Sharpe,A.and Freeman,G.: "PD-L2, a novel B7 homologue, is a second ligand for PD-1 and inhibits T cell activation."Nature Immunol.. (in press). (2001)
• [Publications] Muramatsu,M.,and Honjo,T.: "Complex layers of genetic alteration in generation of antibody diversity."Immunol.Today. 22. 66-68 (2001)
• [Publications] Nishimura,H.,Tanaka,Y.,Okazaki,T.,Nakatani,K.,Hara,M.,Matsumori,A.,Sasayama,S.,Hiai,H.,Minato,N.,and Honjo,T.: "Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice."Science. 291. 319-322 (2001)
• [Publications] Tanigaki,K.,Nogaki,F.,Takahashi,J.,Tashiro,K.,Kurooka,H.,Honjo,T.: "Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate."Neuron. 29. 45-55 (2001)
• [Publications] Watanabe,N.,Ikuta,K.,Fagarasan,S.,Yazumi,S.,Chiba,T.,and Honji,T.: "Migration and differentiation of autoreactive B-1 cells induced by activated γ/δ T cells in antierythrocyte immunoglobulin transgenic mice."J.Exp.Med.. 192. 1577-1586 (2000)
• [Publications] Fagarasan,S.,and Honjo,T.: "T-independent immune response : New aspects of B cell biology."Science. 290. 89-92 (2000)
• [Publications] Freeman,G.j.,Nishimura,H.,(中略) and Honjo,T.: "Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation."J.Exp.Med.. 192. 1027-1034 (2000)
• [Publications] Revy,P.,(中略) Kinoshita,K.,Honjo,T.,Fischer,A.,and Durandy,A.: "Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2)."Cell. 102. 565-575 (2000)
• [Publications] Muramatsu,M.,Kinoshita,K.,Fagarasan,S.,Yamada,S.,Shinkai,Y.,and Honjo,T.: "Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing eazyme."Cell. 102. 553-563 (2000)
• [Publications] Muto,T.,Muramatsu,M.,Taniwaki,M.,Kinoshita,K.and Honjo,T.: "Isolation, tissue distribution and chromosomal localization of the human activation-induced cytidine deaminase (AID) gene."Genomics. 68. 85-88 (2000)
• [Publications] Kamata,T.,Nogaki,F.,Fagarasan,S.,Sakiyama.T.,Kobayashi,I.,Miyawaki,S.,Ikuta,K.,Muso,E.,Yoshida,H.,Sasayama,S.,and Honjo,T.: "Increased frequency of surface IgA-positive plasma cells in the intestinal lamina propria and decreased IgA excretion in hyper IgA (HIGA) mice, a murine model of IgA nephropathy with hyperserum IgA1."J.Immunol.. 165. 1387-1394 (2000)
• [Publications] Kurooka,H.and Honjo,T.: "Functional interaction between the mouse Notch1 intracellular region and histone acetyltransferases PCAF and GCN5."J.Biol.Chem.. 275. 17211-17220 (2000)
• [Publications] Fagarasan,S.,Shinkura,R.,Kamata,T.,Nogaki,F.,Ikuta,K.,Tashiro,K.,and Honjo,T.: "Alymphoplasia (aly)-type nuclear factor κB-inducing kinase (NIK) causes defects in secondary lymphoid tissue chemokine receptor signaling and homing of peritoneal cells to the gut-associated lymphatic tissue system."J.Exp.Med.. 191. 1477-1486 (2000)
• [Publications] Nishimura,H.,Honjo,T.,and Minato,N.: "Facilitation of b selection and modification of positive selection in the thymus of PD-1 deficient mice."J.Exp.Med.. 191. 891-897 (2000)
• [Publications] Miyagawa,F.,Tanaka,Y.,Yamashita,S.and Minato,N.: "Essential requirement of antigen presentation by monocyte-lineage cells for the activation of primary human γδ T cells by aminobisphosphonate antigen."J.Immunol. in press. (2001)
• [Publications] Nishimura,M.,Tanaka,Y.,Okazaki,T.,Nakatani,K.,Hara,M.,Nishio,R.,Matsumori,A.,Hiai,H.,Minato,N.and Honjo,T.: "Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice."Science. 291. 319-322 (2001)
• [Publications] Suga,K.,Katagiri,K.,Harazaki,M.,Kinashi,T.,Hattori,M.and Minato,N.: "CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of."FEBS Letters.. 489. 249-253 (2001)
• [Publications] Kageyama,T.,Nakamura,M.,Matsuo,A.,Yamasaki,Y.,Takakura,Y.,Hashida,M.,Kanai,Y.,Naito,M.,Tsuruo,T.,Minato,N.and Shimohama,S.: "The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier."Brain Res.. 879. 115-121 (2000)
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• [Publications] Nishimura,H.,Honjo,T.and Minato,N.: "Facillitation of β-selection and modification of positive selection in the thymus of PD-deficient mice."J.Exp.Med.. 191. 891-897
• [Publications] Hanyu,M.,Kume,N.,Ikeda,T.,Minami,M.,Kita,T.and Komeda,M.: "VCAM-1 expression precedes macrophage infiltration into subendothelium ofvein grafts interposed into carotid arteries in hypercholesterolemicrabbits-a potential role in vein graft atherosclerosis."Atherosclerosis. (in press). (2001)
• [Publications] Morimoto,M.,Kume,N.,Miyamoto,S.,Ueno,Y.,Kataoka,H.,Minami,M.,Hayashida,K.,Hashimoto,N.and Kita,T: "Lysophosphatidylcholine induces Egr-1 expression and activates the core promoter of PDGF-A chain in vascular endothelial cells."Arterioscler.Thromb.Vasc.Biol.. (in press). (2001)
• [Publications] Kataoka,H.,Kume,N.,Miyamoto,S.,Minami,M.,Morimoto,M.,Hayashida,K.,Hashimoto,N.and Kita.T.: "Oxidized low density lipoprtoein (Ox-LDL) modulates Bax/Bcl-2 through lectin-like Ox-LDL receptor-1 in vascular smooth muscle cells."Arterioscler.Thromb.Vasc.Biol.. (in press). (2001)
• [Publications] Ashida,N.,Arai,H.,Yamasaki,M.and Kita,T.: "Distinct signaling pathways for MCP-1-dependent integrin activation and chemotaxis."J.Biol.Chem.. (in press). (2001)
• [Publications] Yamasaki,M.,Arai,H.,Ashida,N.,Ishii,K.and Kita,T.: "Monocyte chemoattractant protein-1 causes differential proline-rich tyrosin kinase 2-mediated signaling in THP-1 cells."Biochemical J.. (in press). (2001)
• [Publications] Nakatani,J.,Mizuseki,K.,Tsuda,H.,Nakanishi,S.and Sasai,Y.: "Xenopus Xenf : An early endodermal nuclear factor that is regulated in a pathway distinct from Sox17 and Mix-related gene pathways."Mech.Dev.. 91. 81-89 (2000)
• [Publications] Smitt,P.S.,Kinoshita,A.,de Leeuw,B.,Moll,W.,Jaarsma,D.,Henzen-Logmans,S.,Vecht,C.,de Zeeuw,C.,Sekiyama,N.,Nakanishi,S.and Shigemoto,R.: "Hodgkin's disease and ataxia : Passive transfer of autoantibodies that block glutamate receptor mGluR1 causes ataxia in mice."New Eng.J.Med.342 : (2000) 21-27. 342. 21-27 (2000)
• [Publications] Takao,M.,Morigiwa,K.,Sasaki,H.,Miyoshi,T.,Shima,T.,Nakanishi,S.,Nagai,K.and Fukuda,Y.: "Impaired behavioral Suppression by light in the mGluR6-deficient mice."Neuroscience. 97. 779-787 (2000)
• [Publications] Kishi,M.,Mizuseki,K.,Sasai,N.,Yamazaki,H.,Shiota,K.Nakanishi,S.and Sasai,Y.: "Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm."Development. 127. 791-800 (2000)
• [Publications] Matsui,M.,Mizuseki,K.,Nakatani,J.,Nakanishi,S.and Sasai,Y.: "Xenopus Kielin : A dorsalizing factor containing multiple chordin-type repeats secreted from the embryonic midline."Proc.Natl.Acad.Sci.USA. 97. 5291-5296 (2000)
• [Publications] Spooren,W.P.J.M.,Gasparini,F.,van der Putten,H.,Koller,M.,Nakanishi,S.and Kuhn,R.: "Lack of effect of LY314582 (a group 2 metabotropic glutamate receptor agonist) on phencyclidine-induced locomotor activity in metabotropic glutamate receptor 2 knockout mice."Eur.J.Pharmacol.. 397. R1-R2 (2000)
• [Publications] Tomita,K.,Moriyoshi,K.,Nakanishi,S.,Guillmot,F.and Kageyama,R.: "Mammalian achaete-scute and atonal homologs regulate neuronal versus glial fate determination in the central nervous system."EMBO J.19:5460-5472. 19. 5460-5472 (2000)
• [Publications] Kaneko,S.,Hikida,T.,Watanabe,D.,Ichinose,H.,Nagatsu,T.,Kreitman,R.J.,Pastan,I.and Nakanishi,S.: "Synaptic integration mediated by striatal cholinergic interneurons in basal ganglia function."Science. 289. 633-637 (2000)
• [Publications] Tsuji,Y.,Shidama,Y.,Takeshita,T.,Kajimura,N.,Nomura,S.,Sekiyama,N.,Otomo,J.,Usukura,J.,Nakanishi,S.and Jingami,H.: "Cryptic dimer interface and domain organization of the extracellular region of metabotropic glutamate receptor subtype 1."J.Biol.Chem.. 275. 28144-28151 (2000)
• [Publications] Kunishima,N.,Shimaka,Y.,Tsuji,Y.,Sato,T.,Yamamoto,M.,Kumasaka,T.,Nakanishi,S.,Jingami,H.and Morikawa,K.: "Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor."Nature 407 : 971-977.. 407. 971-977 (2000)
• [Publications] Imamura,Y.,Inokawa,H.,Ito,A.,Kadotani,H.,Toyama,K.,Noda,M.,Nakanishi,S.and Hirano,T.: "Roles of GABAergic inhibition and NMDA receptor subunits in the spatio-temporal integration in the cerebellar cortex of mice."Neurosci.Res.. 38. 289-301 (2000)
• [Publications] Kawasaki,H.,Mizuseki,K.,Nishikawa,S.,Kaneko,S.,Kuwana,Y.,Nakanishi,S.,Nishikawa,SI.and Sasai,Y.: "Induction of midbrain dopaminergic neurons from ES cells by stromal cell-drived inducing activity."Neuron 28:31-40. 28. 31-40 (2000)
• [Publications] Yoshida,K.,Watanabe,D.,Ishikane,H.,Tachibana,M.,Pastan,I.and Nakanishi,S.: "A key role of starburst amacrine cells in originating retinal directional selectivity and optokinetic eye movement"Neuron. (in press). (2001)