1999 Fiscal Year Annual Research Report

造血細胞のシグナル伝達

Research Project

Project/Area Number	10181101
Research Institution	The University of Tokyo
Principal Investigator	宮島篤東京大学, 分子細胞生物学研究所, 教授 (50135232)
Co-Investigator(Kenkyū-buntansha)	吉村昭彦久留米大学, 分子生命科学研究所, 教授 (90182815) 田賀哲也東京医科歯科大学, 難治疾患研究所, 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)
Keywords	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
Research Abstract	造血細胞の増殖分化に関わるシグナルリングについての主要な成果は以下のようである。造血幹細胞の前駆細胞ヘマンジオブラストの抗原PCLP1を同定し、PCLP1+CD45-の細胞集団に長期骨髄再構築能があることを示した(宮島)。gp130とGM-CSF受容体のキメラ分子を発現するtransgenic mouseを作成し、GM-CSFによる造血幹細胞増殖を示した(横田)。gp130のシグナル伝達とTGFbによるシグナル伝達のクロストークを示した(田賀)。c-Kitの細胞内アミノ酸残基の置換によりダイマーが形成され恒常的活性化が起こることを示し、IL-3やTPOによる増殖にはRasとSTAT5によるcyclin D1の発現が重要であることも明らかにした(金倉)。サイトカインシグナルの制御因CIS3は赤芽球前駆細胞においてJAK2に会合しEPOのシグナルを抑制する胎児肝造血幹細胞の負の制御因子であるとことを示した(吉村)。抑制型STAT3transgenic mouseを作成し、STAT3が抗癌剤投与による骨髄抑制からの回復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の転写活性化には骨髄細胞特異的なコアクチベーターの関与が示唆された(福永)。

Research Products
(17 results)

All Other

All Publications (17 results)

[Publications] Kinoshita T. et al.: "Hepatic differentiation induced by oncostatin M attenuates fetal liver hematopoiesis."Proc. Natl. Acad. Sci. U.S.A.. 96. 7265-7270 (1999)
[Publications] Hara T. et al.: "Identification of podocalyxin like protein 1 as a novel cell surface marker for hemangioblasts in the murine aorta-gonad-mesonephros region"Immunity. 11. 567-578 (1999)
[Publications] Nakayama K. et al.: "The novel Oncostatin M-Inducible Gene OIG37 Forms a Gene Family with MyD118 and GADD45 and Negative Regulates Cell Growth"J. Biol. Chem.. 274. 24766-24772 (1999)
[Publications] Matusda, T. et al.: "STAT3 activation is sufficient to maintain an undifferentiated state of mouse embrvonic stem cells."EMBO J.. 18. 4261-4269 (1999)
[Publications] Takagi, M. et al.: "Chimeric cytokine receptor can transduce expansion signals in interleukin 6 receptor a (IL-6Ra), IL-11Ra-, and gp 130 low to -negative primitive hematopoietic progenitors"Mol Biol Cell. 10. 3633-3642 (1999)
[Publications] Nishinakamura, R. et al.: "Activation of Stat3 by cytokine receptor gp130 ventralizes Xenopus embryos independent of BMP-4"Dev Biol.. 216. 481-490 (1999)
[Publications] Nakashima, K. et al.: "Synergistic signaling in fetal brain by STAT3- Smad1 complex bridged by p300"Science. 284. 479-482 (2000)
[Publications] Matsumura, I.. et al.: "Increased D-type cyclin expression together with decreased cdc2 activity confers megakaryocytic differentiation of human thrombopoietin-dependent hematopoietic cell line."J. Biol. Chem.. 275. 5553-5559 (2000)
[Publications] 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)
[Publications] Tominaga, S. et al.: "Presence and expression of a novel variant form of ST2 gene production in human leukemic cell line UT-7/GM"Biochem. Biophs. Res. Commum.. 264. 14-18 (1999)
[Publications] Kashii, Y. et al.: "A member of forkhead family transcription factor FKHRL1 is one of the downstream molecule of phosphatidylinositol 30 kinase-Akt activation pathway in erythropoietin signal transduction"Blood in press.
[Publications] Ward AC. et al.: "The jak-stat pathway in normal and perturbed hematopoiesis"Blood. 95. 19-29 (2000)
[Publications] Marine JC. et al.: "SOCS3 Is Essential in the Regulation of Fetal Liver Erythropoiesis"Cell. 98. 617-627 (1999)
[Publications] Marine JC et al.: "SOCS1 Deficiency Causes a Lymphocyte-Dependent Perinatal Lethality"Cell. 98. 609-616 (1999)
[Publications] Mitsui K. et al.: "Cloning and Characterization of a Novel p21 cip1/Waf1-Interacting Zinc Finger Protein, Ciz1"Biochem. Biophs. Res. Commum.. 264. 457-464 (1999)
[Publications] Matsumoto A. et al.: "Suppression of STAT5 Functions I Liver, Mammary Glands, and T Cells in Cytokine-Inducible SH2-Containing Protein 1 Transgenic Mice"Mol. Cell Biol.. 19. 6396-6407 (1999)
[Publications] Sasaki A. et al.: "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase main."Genes to Cells. 4. 339-351 (1999)

1999 Fiscal Year Annual Research Report

造血細胞のシグナル伝達

Principal Investigator

宮島 篤 東京大学, 分子細胞生物学研究所, 教授 (50135232)

Research Products

[Publications] Kinoshita T. et al.: "Hepatic differentiation induced by oncostatin M attenuates fetal liver hematopoiesis."Proc. Natl. Acad. Sci. U.S.A.. 96. 7265-7270 (1999)

[Publications] Hara T. et al.: "Identification of podocalyxin like protein 1 as a novel cell surface marker for hemangioblasts in the murine aorta-gonad-mesonephros region"Immunity. 11. 567-578 (1999)

[Publications] Nakayama K. et al.: "The novel Oncostatin M-Inducible Gene OIG37 Forms a Gene Family with MyD118 and GADD45 and Negative Regulates Cell Growth"J. Biol. Chem.. 274. 24766-24772 (1999)

[Publications] Matusda, T. et al.: "STAT3 activation is sufficient to maintain an undifferentiated state of mouse embrvonic stem cells."EMBO J.. 18. 4261-4269 (1999)

[Publications] Takagi, M. et al.: "Chimeric cytokine receptor can transduce expansion signals in interleukin 6 receptor a (IL-6Ra), IL-11Ra-, and gp 130 low to -negative primitive hematopoietic progenitors"Mol Biol Cell. 10. 3633-3642 (1999)

[Publications] Nishinakamura, R. et al.: "Activation of Stat3 by cytokine receptor gp130 ventralizes Xenopus embryos independent of BMP-4"Dev Biol.. 216. 481-490 (1999)

[Publications] Nakashima, K. et al.: "Synergistic signaling in fetal brain by STAT3- Smad1 complex bridged by p300"Science. 284. 479-482 (2000)

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

[Publications] 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)

[Publications] Tominaga, S. et al.: "Presence and expression of a novel variant form of ST2 gene production in human leukemic cell line UT-7/GM"Biochem. Biophs. Res. Commum.. 264. 14-18 (1999)

[Publications] Kashii, Y. et al.: "A member of forkhead family transcription factor FKHRL1 is one of the downstream molecule of phosphatidylinositol 30 kinase-Akt activation pathway in erythropoietin signal transduction"Blood in press.

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

[Publications] Marine JC. et al.: "SOCS3 Is Essential in the Regulation of Fetal Liver Erythropoiesis"Cell. 98. 617-627 (1999)

[Publications] Marine JC et al.: "SOCS1 Deficiency Causes a Lymphocyte-Dependent Perinatal Lethality"Cell. 98. 609-616 (1999)

[Publications] Mitsui K. et al.: "Cloning and Characterization of a Novel p21 cip1/Waf1-Interacting Zinc Finger Protein, Ciz1"Biochem. Biophs. Res. Commum.. 264. 457-464 (1999)

[Publications] Matsumoto A. et al.: "Suppression of STAT5 Functions I Liver, Mammary Glands, and T Cells in Cytokine-Inducible SH2-Containing Protein 1 Transgenic Mice"Mol. Cell Biol.. 19. 6396-6407 (1999)

[Publications] Sasaki A. et al.: "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase main."Genes to Cells. 4. 339-351 (1999)

宮島篤東京大学, 分子細胞生物学研究所, 教授 (50135232)