2003 年度実績報告書

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

研究課題

研究課題/領域番号	12CE2006
研究機関	京都大学
研究代表者	本庶佑京都大学, 医学研究科, 教授 (80090504)
研究分担者	北徹京都大学, 医学研究科, 教授 (60161460) 湊長博京都大学, 生命科学研究科, 教授 (40137716) 中西重忠京都大学, 生命科学研究科, 教授 (20089105)
キーワード	クラススイッチ / 体細胞突然変異 / AID / PD-1 / PD-L / IMCT法 / パーキンソン / グルタミン酸受容体 / 立体構造
研究概要	本庶は、変異型AIDを網羅的に解析しC末欠損型AIDは体細胞変異誘導活性が欠失するが、クラススィッチ誘導活性は異常である事を見つけ、AIDのC末ドメインにクラススイッチ特異的co-factorがある事を示した。また蛋白合成阻害剤を用いた実験により、AID活性の後に新たな蛋白合成がクラススイッチに必須である事を示しAID活性はDNA編集よりはRNA編集によっている可能性が高い事を示した。AIDを異所性に発現するマウスを作成する事で,AIDの発現制御異常が発ガンにつながる事も示した。自己免疫性拡張性心筋症モデルマウスであるPD-1欠損マウスの解析から、抗トロポニン抗体単独で拡張性心筋症を起こせる事を示し、ヒト心筋症でも自己抗体の関与の可能性を示した。中西らは、1.グルタミン酸神経伝達系において、イオン型と代謝型グルタミン酸受容体並びにイオン型グルタミン酸受容体とカルシウムチャネルが協調的に作用し、時空間的に神経伝達を制御する新しい機構を明らかにした。 2.興奮性神経伝達を部位特異的かつ可逆的に調節できる新しいin vivo(トランスジェニック)の系を確立した。 3.脳発達期における大脳皮質の神経回路の伝達制御機構を明らかにした。 4.側坐核アセチルコリンの手続的記憶と薬物体存誘導における役割を明らかにし、薬物依存症の新しい治療法を堤示した。湊らは、1)SPA-1遺伝子破壊マウスが極めて多彩な骨髄性白血病を発症することを明らかにし、SPA-1が一義的に骨髄造血細胞の癌抑制遺伝子であることを個体レベルで証明した。さらにSPA-1遺伝子欠失により白血病発症に先行してT細胞の機能不全が進行することから、造血系幹細胞の異常増殖能から臨床的骨髄性白血病発症に至る過程において免疫監視機構による抑制機構が極めて重要な役割を果たしていることを強く示唆した。(2)ヒトgdT細胞は胎生期までに一旦高度に多様化したレパートリーを形成するものの、環境中の細菌性非ペプチド低分子抗原によるエピジェネティックな選択により成人期までには同抗原反応性レパートリーに集約され、細菌感染に迅速かつ多クローン性に反応しうる応答様式が形成されることを示した。北らは、動脈硬化の形成・進展機構について研究を進めている。動脈硬化発症には酸化低比重リポ蛋白(LDL)が重要な働きをしているが、我々は2つの酸化LDL受容体LOX-1(Nature,1997)およびSR-PSOX(JBC,2000)を見出している。本年度は、SR-PSOXが心臓の弁を覆う内皮にも発現され、感染性心内膜炎などの急性の炎症性弁膜疾患で強く発現されること、SR-PSOXと結合することによりTリンパ球のVCAM-1への接着能が亢進し、ガンマインターフェロン(IFNg)の発現が誘導されること、などを示した(Yamauchi et al.,Arterioscler Thromb Vasc Biol 2004)。また透過型血小板を用いた系により、血小板凝集にPKCalphaが必須であることを直接的に証明した(Tabuchi et al.,JBC 2003)。また、Munc13-4をSmall GTPase Rab27の標的蛋白質と同定し、Rab27-Munc13-4が血小板濃染顆粒放出を制御していることを明らかにした(Shirakawa et al.,JBC in press)。Rab27とMunc13-4とは細胞障害性T細胞での放出反応に必須であることが別個に証明されており、その機構が注目されていたが、我々の知見はそれに対する解答を与えるものであった。

研究成果
(64件)

すべてその他

すべて文献書誌 (64件)

[文献書誌] Schroeder, T.: "Recombination signal sequence-binding protein Jk alters mesodermal cell fate decisions by suppressing cardiomyogenesis."Proc.Natl.Acad.Sci.USA. 100. 4018-4023 (2003)
[文献書誌] Tanigaki, K.: "Regulation of B cell development by Notch / RBP-J signaling."Semin.Immunol.. 15. 113-119 (2003)
[文献書誌] Okazaki, I.: "Activation-induced cytidine deaminase links class switch recombination and somatic hypermutation."Ann.N.Y.Acad.Sci.. 987. 1-8 (2003)
[文献書誌] Kanatsu-Shinohara, M.: "Functional assessment of self-renewal activity of male germline stem cells following cytotoxic damage and serial transplantation."Biology of Reproduction. 68. 1801-1807 (2003)
[文献書誌] Watanabe, N.: "Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10-deficient mice."Digestive Diseases and Sciences. 48. 408-414 (2003)
[文献書誌] Okazaki, I.: "Constitutive expression of AID leads to tumorigenesis."J.Exp.Med.. 197. 1173-1181 (2003)
[文献書誌] Wang, S.: "Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction."J.Exp.Med.. 197. 1083-1091 (2003)
[文献書誌] Harada, Y.: "Unmutated Immunoglobulin M can protect mice from death by influenza virus infection."J.Exp.Med. 197. 1779-1785 (2003)
[文献書誌] Hatachi, S.: "CD4+PD-1+T cells accumulate as unique anergic cells in rheumatoid arthritis synovial fluid."Journal of Rheumatology. 30. 1410-1419 (2003)
[文献書誌] Iwai, Y.: "PD-1 inhibits antiviral immunity at the effector phase in the liver."J.Exp.Med.. 198. 39-50 (2003)
[文献書誌] Ta, V-T.: "AID mutant analyses implicate requirement for class-switch-specific cofactors."Nature Immunol.. 4. 843-848 (2003)
[文献書誌] Toda, H.: "Stem cell-derived neural stem/progenitor cell supporting factor (SDNSF) is an autocrine/paracrine survival factor for adult neural stem/progenitor cells."J.Biol.Chem.. 278. 35491-35500 (2003)
[文献書誌] Zhu, Y.: "Type two hyper-IgM syndrome caused by mutation in activation-induced cytidine deaminase."J.Med.Dent.Sci.. 50. 41-46 (2003)
[文献書誌] Eto, T.: "RNA-editing cytidine deaminase Apobec-1 is unable to induce somatic hypermutation in mammalian cells."Proc.Natl.Acad.Sci.USA. 100. 12895-12898 (2003)
[文献書誌] Okazaki, T.: "Autoantibodies against cardiac troponin I are responsible for the dilated cardiomyopathy in PD-1 deficient mice."Nature Medicine. 9. 1477-1483 (2003)
[文献書誌] Blank, C.: "Absence of programmed death receptor 1 alters thymic developemnt and enhances generation of CD4/CD8 double-negative TCR-transgenic T cell."J.Immunol. 171. 4574-4581 (2003)
[文献書誌] Suzuki, K.: "Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut."Proc.Natl.Acad.Sci.USA. 101. 1981-1986 (2004)
[文献書誌] Ito, S.: "Activation-induced cytidine deaminase shuttles between nuclues and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1."Proc.Natl.Acad.Sci.USA.. 101. 1975-1980 (2004)
[文献書誌] Amsen, D.: "Antigen presenting cells use the Notch pathway to instruct differentiation of na ve CD4 T cells into the TH2 lineage."Cell. In press.
[文献書誌] Tanigaki, T.: "Regulation of αβ/γδ T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling."Immunity. In press.
[文献書誌] Higashida, H.: "Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells."J.Neurochem.. 85. 1148-1158 (2003)
[文献書誌] Sato, T.: "Amino acid mutagenesis of the ligand binding site and the dimer interface of the metabotropic glutamate receptor 1."J.Biol.Chem.. 278. 4314-4321 (2003)
[文献書誌] Kitano, J.: "Tamalin is a scaffold protein that interacts with multiple neuronal proteins in distinct modes of protein-protein association."J. Biol. Chem. 278. 14762-14768 (2003)
[文献書誌] Jingami, H.: "Structure of the metabotropic glutamate receptor."Curr.Opin.Neurobiol.. 13. 271-278 (2003)
[文献書誌] Hikida, T.: "Acetylcholine enhancement in the nucleus accumbens prevents addictive behaviors of cocaine and morphine."Proc.Natl Acad.Sci.USA. 100. 6169-6173 (2003)
[文献書誌] Kitabatake, Y.: "Impairment of reward-related learning by cholinergic cell ablation in the striatum."Proc.Natl Acad.Sci.USA. 100. 7965-7970 (2003)
[文献書誌] Kitano, J.: "Direct interaction and functional coupling between metabotropic glutamate receptor subtype 1 and voltage-sensitive Cav2.1 Ca2+ channel."J.Biol.Chem.. 278. 25101-25108 (2003)
[文献書誌] Soda, T.: "Segregation and coactivation of developing neocortical layer 1 neurons."J.Neurosci.. 23. 6272-6279 (2003)
[文献書誌] Yamamoto, M.: "Reversible suppression of glutamatergic neurotransmission of cerebellar granule cells In vivo by genetically manipulated expression of tetanus neurotoxin light chain."J.Neurosci.. 23. 6759-6767 (2003)
[文献書誌] Watanabe, D.: "mGluR2 Postsynaptically senses granule cell inputs at Golgi cell synapses."Neuron. 39. 821-829 (2003)
[文献書誌] Kitano, T.: "Characterization of N-methyl-D-aspartate receptor subunits involved in acute ammonia toxicity."Neurochemistry. 44. 83-90 (2004)
[文献書誌] Hattori, M.: "Rap1 GTPase : Functions, regulation, and malignancy."J.Biochem.. 134. 479-484 (2003)
[文献書誌] Kakugawa, K.: "Activation of CEA-CAM-1-mediated cell adhesion via CD98 : Involvement of PKC"FEBS Letters. 552. 184-188 (2003)
[文献書誌] Shen, H-Q.: "T/NK bipotential progenitors in the thymus retain the potential to generate dendritic cells."J.Immunol.. 171. 3401-3406 (2003)
[文献書誌] Ishida, D.: "Antigen-driven T cell anergy and defective memory T cell response via deregulated Rap1 activation in SPA-1-deficient mice."Proc.Natl.Acad.Sci.USA.. 100. 10919-10924 (2003)
[文献書誌] Yamashita, S.: "Recognition Mechanism of Nonpeptide Antigens by Human γδT Cells and their Epigenetic Selection after Birth."Int.Immunol.. 15. 1301-1307 (2003)
[文献書誌] Okazaki, T.: "Autoantibodies against cardiac troponin I are responsible for the dilated cardiomyopathy in PD-1 deficient mice."Nature Med.. 9. 1477-1483 (2003)
[文献書誌] Kato, Y.: "Requirement of species-specific cognate interactions for the activation of human γδT cells by pamidronate."J.Immunol.. 170. 3608-3613 (2003)
[文献書誌] Su, L.: "AF-6 negatively regulates integrin-mediated cell adhesion by binding both Rap1GTP and Rap1 GTPase-activating proteins and enhancing Rap1 inactivation."J.Biol.Chem.. 278. 15232-15238 (2003)
[文献書誌] Ishida, D.: "Myeloproliferative stem cell disorders by deregulated Rap1 activation in SPA-1-deficient mice."Cancer Cell. 4. 55-65 (2003)
[文献書誌] Yamanaka, K.: "Identification of the ubiquitin-protein ligase that recognizes hemeo-xidized IRP2."Nature Cell Biol.. 5. 336-340 (2003)
[文献書誌] Ikawa, T.: "Identification of the earliest prethymic T cell progenitors in murine fetal blood."Blood. 103. 530-537 (2004)
[文献書誌] Kometani, K.: "Rap1 and SPA-1 in hamatologic malignancy."Trends Mol.Med.. in press. (2004)
[文献書誌] Kawamoto, H.: "Cells in Focus : Myeloid cell."Int.J.Biochem.Cell Biol.. in press. (2004)
[文献書誌] Harazaki, M.: "Specific recruitment of SPA-1 to the immunological synapse : Involvement of actin-bundling protein actinin."Immunol.Lett. in press. (2004)
[文献書誌] Kataoka, K.: "LOX-1 Pathway affects the extent of myocardial ischemia-reperfusion injury."Biochem.Biophys.Res.Commun.. 300. 656-660 (2003)
[文献書誌] 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)
[文献書誌] Matsuzawa, Y: "Sustained Reduction of Serum Cholesterol in Low-Dose 6-Year Simvastatin Treatment With Minimum Side Effects in 51,321 Japanese Hypercholesterolemic Patients-Implication of the J-LIT Study,"a Large Scale Nationwide Cohort Study-Circ.J.. 67. 287-294 (2003)
[文献書誌] Nagai, K.: "Growth arrest-specific gene 6 is involved in glomerular hypertrophy in the early stage of diabetic nephropathy."J.Biol.Chem.. 278. 18229-18234 (2003)
[文献書誌] Tanaka, M.: "Donepezil and athetosis in an elderly patient with Alzheimer's disease."J.Am.Geriatr.Soc.. 51. 889-890 (2003)
[文献書誌] Tabuchi A.: "Direct demonstration of involvement of protein kinase Calpha in the Ca2+-induced platelet aggregation."J.Biol.Chem.. 278. 26374-26379 (2003)
[文献書誌] Watanabe T.: "A liver tolerates a portal antigen by generating CD11c+cells, which select Fas ligand+Th2 cells via apoptosis."Hepatology. 38. (2003)
[文献書誌] 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)
[文献書誌] Yanazume T: "Cardiac p300 is involved in myocyte growth with decompensated heart failure."Mol Cell Biol.. 23. 3593-3606 (2003)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Handa T.: "Glomerulonephritis induced by methicillin-sensitive Staphylococcus aureus infection"Clin Exp Nephrol.. 7. 247-249 (2003)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Shirakawa R: "Munc13-4 is a GTP-Rab27 binding protein regulating dense-core granule secretion in platelets."J Biol Chem.. 279. 10730-10737 (2004)
[文献書誌] Xu Y: "Role of Bone Marrow-Derived Progenitor Cells in Cuff-Induced Vascular Injury in Mice."Arterioscler Thromb Vasc Biol.. 24. 477-484 (2004)
[文献書誌] 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)

2003 年度 実績報告書

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

研究代表者

本庶 佑 京都大学, 医学研究科, 教授 (80090504)

研究成果

[文献書誌] Schroeder, T.: "Recombination signal sequence-binding protein Jk alters mesodermal cell fate decisions by suppressing cardiomyogenesis."Proc.Natl.Acad.Sci.USA. 100. 4018-4023 (2003)

[文献書誌] Tanigaki, K.: "Regulation of B cell development by Notch / RBP-J signaling."Semin.Immunol.. 15. 113-119 (2003)

[文献書誌] Okazaki, I.: "Activation-induced cytidine deaminase links class switch recombination and somatic hypermutation."Ann.N.Y.Acad.Sci.. 987. 1-8 (2003)

[文献書誌] Kanatsu-Shinohara, M.: "Functional assessment of self-renewal activity of male germline stem cells following cytotoxic damage and serial transplantation."Biology of Reproduction. 68. 1801-1807 (2003)

[文献書誌] Watanabe, N.: "Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10-deficient mice."Digestive Diseases and Sciences. 48. 408-414 (2003)

[文献書誌] Okazaki, I.: "Constitutive expression of AID leads to tumorigenesis."J.Exp.Med.. 197. 1173-1181 (2003)

[文献書誌] Wang, S.: "Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction."J.Exp.Med.. 197. 1083-1091 (2003)

[文献書誌] Harada, Y.: "Unmutated Immunoglobulin M can protect mice from death by influenza virus infection."J.Exp.Med. 197. 1779-1785 (2003)

[文献書誌] Hatachi, S.: "CD4+PD-1+T cells accumulate as unique anergic cells in rheumatoid arthritis synovial fluid."Journal of Rheumatology. 30. 1410-1419 (2003)

[文献書誌] Iwai, Y.: "PD-1 inhibits antiviral immunity at the effector phase in the liver."J.Exp.Med.. 198. 39-50 (2003)

[文献書誌] Ta, V-T.: "AID mutant analyses implicate requirement for class-switch-specific cofactors."Nature Immunol.. 4. 843-848 (2003)

[文献書誌] Toda, H.: "Stem cell-derived neural stem/progenitor cell supporting factor (SDNSF) is an autocrine/paracrine survival factor for adult neural stem/progenitor cells."J.Biol.Chem.. 278. 35491-35500 (2003)

[文献書誌] Zhu, Y.: "Type two hyper-IgM syndrome caused by mutation in activation-induced cytidine deaminase."J.Med.Dent.Sci.. 50. 41-46 (2003)

[文献書誌] Eto, T.: "RNA-editing cytidine deaminase Apobec-1 is unable to induce somatic hypermutation in mammalian cells."Proc.Natl.Acad.Sci.USA. 100. 12895-12898 (2003)

[文献書誌] Okazaki, T.: "Autoantibodies against cardiac troponin I are responsible for the dilated cardiomyopathy in PD-1 deficient mice."Nature Medicine. 9. 1477-1483 (2003)

[文献書誌] Blank, C.: "Absence of programmed death receptor 1 alters thymic developemnt and enhances generation of CD4/CD8 double-negative TCR-transgenic T cell."J.Immunol. 171. 4574-4581 (2003)

[文献書誌] Suzuki, K.: "Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut."Proc.Natl.Acad.Sci.USA. 101. 1981-1986 (2004)

[文献書誌] Ito, S.: "Activation-induced cytidine deaminase shuttles between nuclues and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1."Proc.Natl.Acad.Sci.USA.. 101. 1975-1980 (2004)

[文献書誌] Amsen, D.: "Antigen presenting cells use the Notch pathway to instruct differentiation of na ve CD4 T cells into the TH2 lineage."Cell. In press.

[文献書誌] Tanigaki, T.: "Regulation of αβ/γδ T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling."Immunity. In press.

[文献書誌] Higashida, H.: "Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells."J.Neurochem.. 85. 1148-1158 (2003)

[文献書誌] Sato, T.: "Amino acid mutagenesis of the ligand binding site and the dimer interface of the metabotropic glutamate receptor 1."J.Biol.Chem.. 278. 4314-4321 (2003)

[文献書誌] Kitano, J.: "Tamalin is a scaffold protein that interacts with multiple neuronal proteins in distinct modes of protein-protein association."J. Biol. Chem. 278. 14762-14768 (2003)

[文献書誌] Jingami, H.: "Structure of the metabotropic glutamate receptor."Curr.Opin.Neurobiol.. 13. 271-278 (2003)

[文献書誌] Hikida, T.: "Acetylcholine enhancement in the nucleus accumbens prevents addictive behaviors of cocaine and morphine."Proc.Natl Acad.Sci.USA. 100. 6169-6173 (2003)

[文献書誌] Kitabatake, Y.: "Impairment of reward-related learning by cholinergic cell ablation in the striatum."Proc.Natl Acad.Sci.USA. 100. 7965-7970 (2003)

[文献書誌] Kitano, J.: "Direct interaction and functional coupling between metabotropic glutamate receptor subtype 1 and voltage-sensitive Cav2.1 Ca2+ channel."J.Biol.Chem.. 278. 25101-25108 (2003)

[文献書誌] Soda, T.: "Segregation and coactivation of developing neocortical layer 1 neurons."J.Neurosci.. 23. 6272-6279 (2003)

[文献書誌] Yamamoto, M.: "Reversible suppression of glutamatergic neurotransmission of cerebellar granule cells In vivo by genetically manipulated expression of tetanus neurotoxin light chain."J.Neurosci.. 23. 6759-6767 (2003)

[文献書誌] Watanabe, D.: "mGluR2 Postsynaptically senses granule cell inputs at Golgi cell synapses."Neuron. 39. 821-829 (2003)

[文献書誌] Kitano, T.: "Characterization of N-methyl-D-aspartate receptor subunits involved in acute ammonia toxicity."Neurochemistry. 44. 83-90 (2004)

[文献書誌] Hattori, M.: "Rap1 GTPase : Functions, regulation, and malignancy."J.Biochem.. 134. 479-484 (2003)

[文献書誌] Kakugawa, K.: "Activation of CEA-CAM-1-mediated cell adhesion via CD98 : Involvement of PKC"FEBS Letters. 552. 184-188 (2003)

[文献書誌] Shen, H-Q.: "T/NK bipotential progenitors in the thymus retain the potential to generate dendritic cells."J.Immunol.. 171. 3401-3406 (2003)

[文献書誌] Ishida, D.: "Antigen-driven T cell anergy and defective memory T cell response via deregulated Rap1 activation in SPA-1-deficient mice."Proc.Natl.Acad.Sci.USA.. 100. 10919-10924 (2003)

[文献書誌] Yamashita, S.: "Recognition Mechanism of Nonpeptide Antigens by Human γδT Cells and their Epigenetic Selection after Birth."Int.Immunol.. 15. 1301-1307 (2003)

[文献書誌] Okazaki, T.: "Autoantibodies against cardiac troponin I are responsible for the dilated cardiomyopathy in PD-1 deficient mice."Nature Med.. 9. 1477-1483 (2003)

[文献書誌] Kato, Y.: "Requirement of species-specific cognate interactions for the activation of human γδT cells by pamidronate."J.Immunol.. 170. 3608-3613 (2003)

[文献書誌] Su, L.: "AF-6 negatively regulates integrin-mediated cell adhesion by binding both Rap1GTP and Rap1 GTPase-activating proteins and enhancing Rap1 inactivation."J.Biol.Chem.. 278. 15232-15238 (2003)

[文献書誌] Ishida, D.: "Myeloproliferative stem cell disorders by deregulated Rap1 activation in SPA-1-deficient mice."Cancer Cell. 4. 55-65 (2003)

[文献書誌] Yamanaka, K.: "Identification of the ubiquitin-protein ligase that recognizes hemeo-xidized IRP2."Nature Cell Biol.. 5. 336-340 (2003)

[文献書誌] Ikawa, T.: "Identification of the earliest prethymic T cell progenitors in murine fetal blood."Blood. 103. 530-537 (2004)

[文献書誌] Kometani, K.: "Rap1 and SPA-1 in hamatologic malignancy."Trends Mol.Med.. in press. (2004)

[文献書誌] Kawamoto, H.: "Cells in Focus : Myeloid cell."Int.J.Biochem.Cell Biol.. in press. (2004)

[文献書誌] Harazaki, M.: "Specific recruitment of SPA-1 to the immunological synapse : Involvement of actin-bundling protein actinin."Immunol.Lett. in press. (2004)

[文献書誌] Kataoka, K.: "LOX-1 Pathway affects the extent of myocardial ischemia-reperfusion injury."Biochem.Biophys.Res.Commun.. 300. 656-660 (2003)

[文献書誌] 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)

[文献書誌] Matsuzawa, Y: "Sustained Reduction of Serum Cholesterol in Low-Dose 6-Year Simvastatin Treatment With Minimum Side Effects in 51,321 Japanese Hypercholesterolemic Patients-Implication of the J-LIT Study,"a Large Scale Nationwide Cohort Study-Circ.J.. 67. 287-294 (2003)

[文献書誌] Nagai, K.: "Growth arrest-specific gene 6 is involved in glomerular hypertrophy in the early stage of diabetic nephropathy."J.Biol.Chem.. 278. 18229-18234 (2003)

[文献書誌] Tanaka, M.: "Donepezil and athetosis in an elderly patient with Alzheimer's disease."J.Am.Geriatr.Soc.. 51. 889-890 (2003)

[文献書誌] Tabuchi A.: "Direct demonstration of involvement of protein kinase Calpha in the Ca2+-induced platelet aggregation."J.Biol.Chem.. 278. 26374-26379 (2003)

[文献書誌] Watanabe T.: "A liver tolerates a portal antigen by generating CD11c+cells, which select Fas ligand+Th2 cells via apoptosis."Hepatology. 38. (2003)

[文献書誌] 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)

[文献書誌] Yanazume T: "Cardiac p300 is involved in myocyte growth with decompensated heart failure."Mol Cell Biol.. 23. 3593-3606 (2003)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] Handa T.: "Glomerulonephritis induced by methicillin-sensitive Staphylococcus aureus infection"Clin Exp Nephrol.. 7. 247-249 (2003)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] Shirakawa R: "Munc13-4 is a GTP-Rab27 binding protein regulating dense-core granule secretion in platelets."J Biol Chem.. 279. 10730-10737 (2004)

[文献書誌] Xu Y: "Role of Bone Marrow-Derived Progenitor Cells in Cuff-Induced Vascular Injury in Mice."Arterioscler Thromb Vasc Biol.. 24. 477-484 (2004)

[文献書誌] 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)

2003 年度実績報告書

本庶佑京都大学, 医学研究科, 教授 (80090504)