2000 年度実績報告書

造血細胞のシグナル伝達

研究課題

研究課題/領域番号	10181101
研究機関	東京大学
研究代表者	宮島篤東京大学, 分子細胞生物学研究所, 教授 (50135232)
研究分担者	吉村昭彦久留米大学, 分子生命科学研究所, 教授 (90182815) 田賀哲也熊本大学, 発生医学研究センター, 教授 (40192629) 福永理己郎大阪大学, 医学部, 助教授 (40189965) 金倉譲大阪大学, 医学部, 教授 (20177489) 横田崇東京大学, 医科学研究所, 客員教授 (50134622)
キーワード	造血因子 / サイトカイン / シグナル伝達 / 受容体 / キナーゼ / 転写因子 / 細胞増殖 / 細胞分化
研究概要	造血細胞の増殖分化に関わるシグナルについての主な成果は以下のようである。 AGM領域で発生した造血幹細胞が胎生肝臓で増幅するin vitro系を確立した。胎生肝臓の分化にはSTAT3依存性と非依存性の機構があることを見いだした(宮島)。gp130とGM-CSF受容体のキメラ分子を発現するtransgenic mouseの造血幹細胞がc-Kitとgp130を同時に活性化することで自己複製する可能性を示した(横田)。初期造血に関与するシグナル分子を探索し、胎児造血組織で発現する核移行配列を有する新規分子ELYSを得た(田賀)。巨核球が多倍体化する際にG2/M期特異的に発現するAIMキナーゼの発現が低下が必要かつ充分であることが示唆された(金倉)。白血病の染色体転座から発見されたTEL・JAK2の癌化能をJABが抑制することを見いだした。その際、SOCS-boxを介したユビキチン/プロテアソーム系によるキナーゼの分解が抑制に重要であることを示した(吉村)。GATA1プロモーターに抑制型STAT3を連結したtransgenic mouseを作成し、STAT3が赤血球・巨核球系前駆細胞の増幅に重要であることを示した(小松)。好中球の増殖分化に関与する転写因子MZF-2の転写活性化ドメインがMAPキナーゼでリン酸化され、負の制御を受けることが示唆された(福永)。

研究成果
(26件)

すべてその他

すべて文献書誌 (26件)

[文献書誌] Ito Y. et al.: "Retroviral gene transfer of signaling molecules into murine fetal hepatocytes defines distinct roles for the STAT3 and Ras pathways during hepatic development."Hepatology. 32. 1370-1376 (2000)
[文献書誌] Kojima N. et al.: "Cell-density-dependent regulation of hepatic development by a gp 130-independent pathway"Biochem.Biophys.Res.Commun. 277. 152-158 (2000)
[文献書誌] Miyajima A. et al.: "Roles of Oncostatin M in hematopoiesis and liver development."Cytokine and Growth Factor Reviews. 11. 177-183 (2000)
[文献書誌] Sato A. et al.: "Cloning and expression pattern of a Xenopus pronephros-specific gene, XSMP-30"Mechanism of Development. 92. 273-275 (2000)
[文献書誌] Nakayama,N. et al.: "A novel chordin-like protein inhibitor for bone morphogenetic proteins"Blood.. (in press). (2001)
[文献書誌] Matsumura,I. et al.: "Increased D-type cyclin expression together with decreased cdc2 activity confers megakaryocytic differentiation of a human thrombopoietin-dependent hematopoietic cell line"J.Biol.Chem.. 275. 5553-5559 (2000)
[文献書誌] Sakamoto H. et al.: "Mitogen-Activated Protein Kinase Plays an Essential Role in the Erythropoietin-Dependent Proliferation of CTLL-2 Cells"J.Biol.Chem.. 275. 35857-35862 (2000)
[文献書誌] Sasaki A. et al.: "CIS3/SOCS3 suppresses erythropoietin signaling by binding the EPO receptor and JAK2"J.Biol.Chem.. 275. 29338-29347 (2000)
[文献書誌] Yasukawa H. et al.: "Negative Regulation of Cytokine Signaling Pathways"Annu.Rev.Immunol.. 18. 143-164 (2000)
[文献書誌] Ward AC. et al.: "The jak-stat pathway in normal and perturbed hematopoiesis"Blood. 95. 19-29 (2000)
[文献書誌] M.Yanagisawa et al.: "Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gpl30, and a transcription factor, STAT3"J.Neurochem. 74. 1498-1504 (2000)
[文献書誌] N.Kimura et al.: "BMP2-induced apoptosis is mediated by activation of TAK1-p38 kinase pathway that is negatively regulated by Smad6"J.Biol.Chem.. 275. 17647-17652 (2000)
[文献書誌] M.Yanagisawa et al.: "Signaling crosstalk underlying synergistic induction of astrocyte differentiation by BMPs and IL-6 family of cytokines"FEBS Lett.. 24546. 1-5 (2001)
[文献書誌] Kashii,Y. et al.: "A member of forkhead family transcription factor FKHRL1 is one of the downstream molecule of phosphatidylinositol 3-kinaze-Akt activation pathway in erythropoietin signal transduction"Blood. 96. 941-949 (2000)
[文献書誌] Tanaka,H. et al.: "GATA-1 blocks interleukin-6 induced macrophage differentiation and apoptosis through the sustained expression of cyclin D1 and bcl-2 in a murine myeloid cell line M1"Blood. 95. 1264-1273 (2000)
[文献書誌] Daino,H. et al.: "Induction of apoptosis by extracellular ubiquitin in human hematopoietic cells : possible involvement of Stat3 degradation by proteasome pathway in interleukin 6-dependent hematopoietic cells."Blood. 95. 2577-2585 (2000)
[文献書誌] Odajima,J. et al.: "Full oncogenic activities of v-Src are mediated by cooperation of multiple signaling pathways ; ras as an essential mediator for cell survival"J.Biol.Chem.. 275. 24096-24105 (2000)
[文献書誌] Matsumura,I. et al.: "Biological significance of GATA-1 activities in ras-mediated megakaryocytic differentiation of hematopoietic cell lines"Blood. 96. 2440-2450 (2000)
[文献書誌] Mizuki,M. et al.: "Transformation of 32D cells by Flt3 mutations from AML patients is mediated by the Ras And STAT5 pathways"Blood. 96. 3907-3914 (2000)
[文献書誌] Kawasaki,A. et al.: "Down-regulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells"J.Cell Biol. 152. 275-287 (2001)
[文献書誌] Suzuki A. et al.: "CIS3/SOCS3/SSI3 Plays a Negative Regulatory Role in STAT3 Activation and Intestinal Inflammation"J.Exp.Med.. (in press). (2001)
[文献書誌] Kamizono S. et al.: "The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2"J.Biol.Chem.. (in press). (2001)
[文献書誌] Uchida,M. et al.: "A functional role of mitogen-activated protein kinaze, Erk1 and Erk2, in the differentiation of a human leukemia cell line UT-7/GM : a possible key factor for cell fate determination toward erythroid and megakaryocytic lineages"Int.Haematol.. 73. 78-83 (2001)
[文献書誌] Kirito,K. et al.: "Identification of a novel Stat1 and Stat3 activation motif within the erythropoietin receptor"Blood.. (in press). (2001)
[文献書誌] Tanaka,M. et al.: "Forkhead family transcription factor FKHRL1 regulates cell cycle of megakaryocytic cells as a downstream molecule of TPO signaling"J.Biol.Chem.. (in press). (2001)
[文献書誌] Hefner,Y. et al.: "Serine 727 Phosphorylation and Activation of Cytosolic Phospholipase A2 by MNK1-related Protein Kinases"J.Biol.Chem.. 275. 37542-37551 (2000)

2000 年度 実績報告書

造血細胞のシグナル伝達

研究代表者

宮島 篤 東京大学, 分子細胞生物学研究所, 教授 (50135232)

研究成果

[文献書誌] Ito Y. et al.: "Retroviral gene transfer of signaling molecules into murine fetal hepatocytes defines distinct roles for the STAT3 and Ras pathways during hepatic development."Hepatology. 32. 1370-1376 (2000)

[文献書誌] Kojima N. et al.: "Cell-density-dependent regulation of hepatic development by a gp 130-independent pathway"Biochem.Biophys.Res.Commun. 277. 152-158 (2000)

[文献書誌] Miyajima A. et al.: "Roles of Oncostatin M in hematopoiesis and liver development."Cytokine and Growth Factor Reviews. 11. 177-183 (2000)

[文献書誌] Sato A. et al.: "Cloning and expression pattern of a Xenopus pronephros-specific gene, XSMP-30"Mechanism of Development. 92. 273-275 (2000)

[文献書誌] Nakayama,N. et al.: "A novel chordin-like protein inhibitor for bone morphogenetic proteins"Blood.. (in press). (2001)

[文献書誌] Matsumura,I. et al.: "Increased D-type cyclin expression together with decreased cdc2 activity confers megakaryocytic differentiation of a human thrombopoietin-dependent hematopoietic cell line"J.Biol.Chem.. 275. 5553-5559 (2000)

[文献書誌] Sakamoto H. et al.: "Mitogen-Activated Protein Kinase Plays an Essential Role in the Erythropoietin-Dependent Proliferation of CTLL-2 Cells"J.Biol.Chem.. 275. 35857-35862 (2000)

[文献書誌] Sasaki A. et al.: "CIS3/SOCS3 suppresses erythropoietin signaling by binding the EPO receptor and JAK2"J.Biol.Chem.. 275. 29338-29347 (2000)

[文献書誌] Yasukawa H. et al.: "Negative Regulation of Cytokine Signaling Pathways"Annu.Rev.Immunol.. 18. 143-164 (2000)

[文献書誌] Ward AC. et al.: "The jak-stat pathway in normal and perturbed hematopoiesis"Blood. 95. 19-29 (2000)

[文献書誌] M.Yanagisawa et al.: "Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gpl30, and a transcription factor, STAT3"J.Neurochem. 74. 1498-1504 (2000)

[文献書誌] N.Kimura et al.: "BMP2-induced apoptosis is mediated by activation of TAK1-p38 kinase pathway that is negatively regulated by Smad6"J.Biol.Chem.. 275. 17647-17652 (2000)

[文献書誌] M.Yanagisawa et al.: "Signaling crosstalk underlying synergistic induction of astrocyte differentiation by BMPs and IL-6 family of cytokines"FEBS Lett.. 24546. 1-5 (2001)

[文献書誌] Kashii,Y. et al.: "A member of forkhead family transcription factor FKHRL1 is one of the downstream molecule of phosphatidylinositol 3-kinaze-Akt activation pathway in erythropoietin signal transduction"Blood. 96. 941-949 (2000)

[文献書誌] Tanaka,H. et al.: "GATA-1 blocks interleukin-6 induced macrophage differentiation and apoptosis through the sustained expression of cyclin D1 and bcl-2 in a murine myeloid cell line M1"Blood. 95. 1264-1273 (2000)

[文献書誌] Daino,H. et al.: "Induction of apoptosis by extracellular ubiquitin in human hematopoietic cells : possible involvement of Stat3 degradation by proteasome pathway in interleukin 6-dependent hematopoietic cells."Blood. 95. 2577-2585 (2000)

[文献書誌] Odajima,J. et al.: "Full oncogenic activities of v-Src are mediated by cooperation of multiple signaling pathways ; ras as an essential mediator for cell survival"J.Biol.Chem.. 275. 24096-24105 (2000)

[文献書誌] Matsumura,I. et al.: "Biological significance of GATA-1 activities in ras-mediated megakaryocytic differentiation of hematopoietic cell lines"Blood. 96. 2440-2450 (2000)

[文献書誌] Mizuki,M. et al.: "Transformation of 32D cells by Flt3 mutations from AML patients is mediated by the Ras And STAT5 pathways"Blood. 96. 3907-3914 (2000)

[文献書誌] Kawasaki,A. et al.: "Down-regulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells"J.Cell Biol. 152. 275-287 (2001)

[文献書誌] Suzuki A. et al.: "CIS3/SOCS3/SSI3 Plays a Negative Regulatory Role in STAT3 Activation and Intestinal Inflammation"J.Exp.Med.. (in press). (2001)

[文献書誌] Kamizono S. et al.: "The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2"J.Biol.Chem.. (in press). (2001)

[文献書誌] Uchida,M. et al.: "A functional role of mitogen-activated protein kinaze, Erk1 and Erk2, in the differentiation of a human leukemia cell line UT-7/GM : a possible key factor for cell fate determination toward erythroid and megakaryocytic lineages"Int.Haematol.. 73. 78-83 (2001)

[文献書誌] Kirito,K. et al.: "Identification of a novel Stat1 and Stat3 activation motif within the erythropoietin receptor"Blood.. (in press). (2001)

[文献書誌] Tanaka,M. et al.: "Forkhead family transcription factor FKHRL1 regulates cell cycle of megakaryocytic cells as a downstream molecule of TPO signaling"J.Biol.Chem.. (in press). (2001)

[文献書誌] Hefner,Y. et al.: "Serine 727 Phosphorylation and Activation of Cytosolic Phospholipase A2 by MNK1-related Protein Kinases"J.Biol.Chem.. 275. 37542-37551 (2000)

2000 年度実績報告書

宮島篤東京大学, 分子細胞生物学研究所, 教授 (50135232)