2000 年度実績報告書

抗原認識のシグナル変換

研究課題

研究課題/領域番号	12051101
研究種目	特定領域研究(A)
研究機関	千葉大学
研究代表者	斉藤隆千葉大学, 大学院・医学研究所, 教授 (50205655)
研究分担者	渡邊武九州大学, 生体防御医学研究所, 教授 (40028684) 黒崎知博関西医科大学, 医学部, 教授 (50178125)
キーワード	BLNK / BCAP / PLC-γ欠損マウス / LAT / プレB細胞 / Lyn欠損マウス / Gab-2 / CTLA-4
研究概要	本特定研究調整班は、予定通り今年度2度にわたって情報交換のための討論会としての会合を持ち、調整班の目的である相互の研究の進行状況と交流について話し合ってきた。実験条件の統一化・標準化のためのDNAシーケンサーも順調に稼働している。研究内容としては、本調整班が、T細胞とB細胞の認識とシグナル伝達系の解析とその異常な制御に基づく免疫疾患の機序の解析を目指していることから、T・B細胞での共通性、相互のクロストーク、共通な制御系、などの解明と疾患に至るメカニズムの共通性と独自性の解析を中心的に考えてきた。T細胞ではCTLA-4の様な細胞表面レセプターによる負の制御とGab-2のような細胞内シグナル分子による制御の2種類が明らかになり(斉藤)、B細胞において見いだした特異的な負のシグナル調節機構(渡邊)と比較する形となった。更にT細胞でのLAT,SLP-76の活性化機構とB細胞でのBLNKを介するシグナル系の比較検討から新しいメカニズムを明らかにした(黒崎)。T細胞では成熟T細胞がシグナル伝達の中心に用いるLATに関して、B細胞では未熟細胞でのみ発現し、正ではなく負に働いている、という興味ある発見をした(渡邊)。これらは、多くがT細胞とB細胞において、全体としては同様なシステムを使用しているものの、それぞれの異なる制御系を発達させていることを明らかにした。こうした相互の解析を進めるために、調整班では共通試薬の共同管理・交換を行った。また、相互の情報の日常的交換のための連絡網としてのネットワークを作り、迅速な研究支援体制を構築しつつある。

研究成果

(34件)

すべてその他

すべて文献書誌 (34件)

[文献書誌] Suzuki,K.: "Janus kinase 3(Jak 3)is essential for common cytokine receptor γ chain(γc)-dependent signaling : comparative analysis of γc, Jak3, and γc and Jak3 double deficient mice."Int.Immunol.. 12. 123-132 (2000)
[文献書誌] Fossati-Jimack,L.: "Markedly different pathogenicity of four immunoguloblin G isotype-switch variants of an antierythrocyte autoantibody is based on their capacity to interact in vivo with low-affinity Fcγ receptor III."J.Exp.Med.. 191. 1293-1302 (2000)
[文献書誌] Hamano,Y.: "Immune complex and Fc receptor-mediated augmentation of antigen presentation for in vivo helper T cell responses."J.Immunol.. 164. 6113-6119 (2000)
[文献書誌] Nakatsu,F.: "A di-leucine signal in the ubiquitin moiety : possible involvement in ubiquitination-mediated endocytosis."J.Biol.Chem.. 275. 26213-26219 (2000)
[文献書誌] Tsujino,S.: "Differential requirement of the cytoplasmic subregions of γc chain in T cell development and function."Proc.Natl.Acad.Sci.USA. 97. 10514-10519 (2000)
[文献書誌] Suzuki,K.: "Role of common cytokine receptor γ chain(γc)-and Jak3-dependent signaling in the proliferation and survival of murine mast cells."Blood. 96. 2172-2180 (2000)
[文献書誌] Iida,T.: "Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4^+ T cells."J.Immunol.. 165. 5062-5068 (2000)
[文献書誌] Okazaki,Y.: "Cell surface expression of calnexin, a molecular chaperone in the endoplasmic reticulum."J.Biol.Chem.. 275. 35751-35758 (2000)
[文献書誌] Watanabe,N.: "The quantity of TCR signaling determines positive selection and commitment of T cells."J.Immunol.. 165. 6252-6261 (2000)
[文献書誌] Arase,H.: "Negative regulation of expression and function of FcγRIII by CD3ζ in murine NK cells."J.Immunol.. 166. 21-25 (2001)
[文献書誌] Okada,T.: "BCAP : The tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation."Immunity. 13. 817-827 (2000)
[文献書誌] Ishiai,M.: "Involvement of LAT, Gads, and GRb2 in compartmentation of SLP-76 to the plasma membrane."J.Exp.Med.. 192. 847-856 (2000)
[文献書誌] Hashimoto,A.: "Essential role of phospholopase C-γ2 in B cell development and function."J.Immunol.. 165. 1738-1742 (2000)
[文献書誌] Yasuda,T.: "Cb1 suppresses B cell receptor-mediated phospholipase C(PLC)-γ2 activation by regulating B cell linker protein-PLC-γ2 binding."J.Exp.Med.. 191. 641-650 (2000)
[文献書誌] Kurosaki,T.: "BLNK : Connecting Syk and Btk to calcium signals."Immunity. 12. 1-5 (2000)
[文献書誌] Kurosaki,T.: "Functional dissection of BCR signaling pathways"Curr.Opin.Immunol.. 12. 276-281 (2000)
[文献書誌] Liou,J.: "HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1."Immunity. 12. 399-408 (2000)
[文献書誌] Wong,J.: "Functional complementation of BLNK by SLP-76 and LAT linker proteins."J.Biol.Chem.. 275. 33116-33122 (2000)
[文献書誌] Pogue,S.L.: "B cell antigen receptor-induced activation of Akt promotes B cell survival and is dependent on Syk kinase."J.Immunol.. 165. 1300-1306 (2000)
[文献書誌] Grishin,A.: "Involvement of Shc and Cb1-PI 3-kinase in Lyn-dependent proliferative signalling pathways for G-CSF."Oncogene. 19. 97-105 (2000)
[文献書誌] Burrows,P.D.: "Activation of self-reactive B cells and autoimmune diseases."Reviews in Immunogenetics. 2. 38-51 (2000)
[文献書誌] Yayoshi-Yamamoto,S.: "FRL, a novel member of Formin-related proteins, that binds to Rac and regulates cell motility and survival of macrophages."Mol.Cel.Biol.. 20. 6872-6881 (2000)
[文献書誌] Ochi,H.: "Negative regulation of BCR-mediated signaling in B-1 cells through CD5 and Ly49 coreceptors via Lyn kinase activity."Int.Immunol.. 12. 1417-1423 (2000)
[文献書誌] Kondo,S.: "Suppression of insulitis and diabetes in B cell-deficient mice treated with streptozocin : b cells are essential for the T cell receptor clonotype spreading of islet-infiltrating T cells."Int.Immunol.. 12. 1075-1083 (2000)
[文献書誌] Kobayashi,T.: "Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor-deficient mice."J.Clin.Invest.. 105. 1741-1749 (2000)
[文献書誌] Marguet,D.: "Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26."Proc.Natl.Acad.Sci.USA. 97. 6874-6879 (2000)
[文献書誌] Sonoda,K.: "The clinical significance of tumor-associated antigen RCAS1 expression in the normal, hyperplastic, and malignant uterine endometrium"Gynecol.Oncol.. 79. 424-429 (2000)
[文献書誌] Iwasaki,T.: "The expression of human tumor-associated antigen RCAS1 and the prognostic significance in lung cancer."Int.J.Cancer. 89. 488-493 (2000)
[文献書誌] Nakahara,H.: "Vascular permeability in allergic conjunctivitis in mice lacking histamine H1 receptors."Eur.J.Pharmacol.. 409. 313-317 (2000)
[文献書誌] Izumizaki,M.: "Lack of temperature-induced polypnea in histamine H1 receptor-deficient mice."Neurosci.Lett. 284. 139-142 (2000)
[文献書誌] Mobarakeh,J.I.: "Role of histamine H1 receptor in pain perception : a study of the receptor gene knockout mice."Eur.J.Pharmacol.. 391. 81-89 (2000)
[文献書誌] Ohshima,K.: "Expression of RCAS1 and FasL in human trophoblasts and uterine glands during pregnancy ; the possible role in immune privilege."Clin.Exp.Immunol.. (In press).
[文献書誌] Masaki,T.: "Targeted disruption of histamine H1 receptor attenuated regulatory effect of leptin on feeding behavior, adiposity and UCP family expression in mice."Diabetes. (In press).
[文献書誌] Masaki,T.: "Central infusion of hitamine reduced fat accumulation and increased UCP family expression in leptin resistant obese mice."Diabetes. (In press).

2000 年度 実績報告書

抗原認識のシグナル変換

研究代表者

斉藤 隆 千葉大学, 大学院・医学研究所, 教授 (50205655)

研究成果

[文献書誌] Suzuki,K.: "Janus kinase 3(Jak 3)is essential for common cytokine receptor γ chain(γc)-dependent signaling : comparative analysis of γc, Jak3, and γc and Jak3 double deficient mice."Int.Immunol.. 12. 123-132 (2000)

[文献書誌] Fossati-Jimack,L.: "Markedly different pathogenicity of four immunoguloblin G isotype-switch variants of an antierythrocyte autoantibody is based on their capacity to interact in vivo with low-affinity Fcγ receptor III."J.Exp.Med.. 191. 1293-1302 (2000)

[文献書誌] Hamano,Y.: "Immune complex and Fc receptor-mediated augmentation of antigen presentation for in vivo helper T cell responses."J.Immunol.. 164. 6113-6119 (2000)

[文献書誌] Nakatsu,F.: "A di-leucine signal in the ubiquitin moiety : possible involvement in ubiquitination-mediated endocytosis."J.Biol.Chem.. 275. 26213-26219 (2000)

[文献書誌] Tsujino,S.: "Differential requirement of the cytoplasmic subregions of γc chain in T cell development and function."Proc.Natl.Acad.Sci.USA. 97. 10514-10519 (2000)

[文献書誌] Suzuki,K.: "Role of common cytokine receptor γ chain(γc)-and Jak3-dependent signaling in the proliferation and survival of murine mast cells."Blood. 96. 2172-2180 (2000)

[文献書誌] Iida,T.: "Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4^+ T cells."J.Immunol.. 165. 5062-5068 (2000)

[文献書誌] Okazaki,Y.: "Cell surface expression of calnexin, a molecular chaperone in the endoplasmic reticulum."J.Biol.Chem.. 275. 35751-35758 (2000)

[文献書誌] Watanabe,N.: "The quantity of TCR signaling determines positive selection and commitment of T cells."J.Immunol.. 165. 6252-6261 (2000)

[文献書誌] Arase,H.: "Negative regulation of expression and function of FcγRIII by CD3ζ in murine NK cells."J.Immunol.. 166. 21-25 (2001)

[文献書誌] Okada,T.: "BCAP : The tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation."Immunity. 13. 817-827 (2000)

[文献書誌] Ishiai,M.: "Involvement of LAT, Gads, and GRb2 in compartmentation of SLP-76 to the plasma membrane."J.Exp.Med.. 192. 847-856 (2000)

[文献書誌] Hashimoto,A.: "Essential role of phospholopase C-γ2 in B cell development and function."J.Immunol.. 165. 1738-1742 (2000)

[文献書誌] Yasuda,T.: "Cb1 suppresses B cell receptor-mediated phospholipase C(PLC)-γ2 activation by regulating B cell linker protein-PLC-γ2 binding."J.Exp.Med.. 191. 641-650 (2000)

[文献書誌] Kurosaki,T.: "BLNK : Connecting Syk and Btk to calcium signals."Immunity. 12. 1-5 (2000)

[文献書誌] Kurosaki,T.: "Functional dissection of BCR signaling pathways"Curr.Opin.Immunol.. 12. 276-281 (2000)

[文献書誌] Liou,J.: "HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1."Immunity. 12. 399-408 (2000)

[文献書誌] Wong,J.: "Functional complementation of BLNK by SLP-76 and LAT linker proteins."J.Biol.Chem.. 275. 33116-33122 (2000)

[文献書誌] Pogue,S.L.: "B cell antigen receptor-induced activation of Akt promotes B cell survival and is dependent on Syk kinase."J.Immunol.. 165. 1300-1306 (2000)

[文献書誌] Grishin,A.: "Involvement of Shc and Cb1-PI 3-kinase in Lyn-dependent proliferative signalling pathways for G-CSF."Oncogene. 19. 97-105 (2000)

[文献書誌] Burrows,P.D.: "Activation of self-reactive B cells and autoimmune diseases."Reviews in Immunogenetics. 2. 38-51 (2000)

[文献書誌] Yayoshi-Yamamoto,S.: "FRL, a novel member of Formin-related proteins, that binds to Rac and regulates cell motility and survival of macrophages."Mol.Cel.Biol.. 20. 6872-6881 (2000)

[文献書誌] Ochi,H.: "Negative regulation of BCR-mediated signaling in B-1 cells through CD5 and Ly49 coreceptors via Lyn kinase activity."Int.Immunol.. 12. 1417-1423 (2000)

[文献書誌] Kondo,S.: "Suppression of insulitis and diabetes in B cell-deficient mice treated with streptozocin : b cells are essential for the T cell receptor clonotype spreading of islet-infiltrating T cells."Int.Immunol.. 12. 1075-1083 (2000)

[文献書誌] Kobayashi,T.: "Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor-deficient mice."J.Clin.Invest.. 105. 1741-1749 (2000)

[文献書誌] Marguet,D.: "Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26."Proc.Natl.Acad.Sci.USA. 97. 6874-6879 (2000)

[文献書誌] Sonoda,K.: "The clinical significance of tumor-associated antigen RCAS1 expression in the normal, hyperplastic, and malignant uterine endometrium"Gynecol.Oncol.. 79. 424-429 (2000)

[文献書誌] Iwasaki,T.: "The expression of human tumor-associated antigen RCAS1 and the prognostic significance in lung cancer."Int.J.Cancer. 89. 488-493 (2000)

[文献書誌] Nakahara,H.: "Vascular permeability in allergic conjunctivitis in mice lacking histamine H1 receptors."Eur.J.Pharmacol.. 409. 313-317 (2000)

[文献書誌] Izumizaki,M.: "Lack of temperature-induced polypnea in histamine H1 receptor-deficient mice."Neurosci.Lett. 284. 139-142 (2000)

[文献書誌] Mobarakeh,J.I.: "Role of histamine H1 receptor in pain perception : a study of the receptor gene knockout mice."Eur.J.Pharmacol.. 391. 81-89 (2000)

[文献書誌] Ohshima,K.: "Expression of RCAS1 and FasL in human trophoblasts and uterine glands during pregnancy ; the possible role in immune privilege."Clin.Exp.Immunol.. (In press).

[文献書誌] Masaki,T.: "Targeted disruption of histamine H1 receptor attenuated regulatory effect of leptin on feeding behavior, adiposity and UCP family expression in mice."Diabetes. (In press).

[文献書誌] Masaki,T.: "Central infusion of hitamine reduced fat accumulation and increased UCP family expression in leptin resistant obese mice."Diabetes. (In press).

2000 年度実績報告書

斉藤隆千葉大学, 大学院・医学研究所, 教授 (50205655)