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analysis of molecular mechanism of hematopoiesis and hematological disorders

Research Project

Project/Area Number 09470233
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionJich Medical School

Principal Investigator

KOMATSU Norio  Jich. Medical School, Dept. of Medicine, Assistant Professor, 医学部, 講師 (50186798)

Co-Investigator(Kenkyū-buntansha) KASHII Yoshifumi  Jich. Medical School, Dept. of Medicine, Assistant Professor, 医学部, 助手 (10271222)
UCHIDA Mie  Jich. Medical School, Dept. of Medicine, Assistant Professor, 医学部, 助手 (80316520)
KIRITO Keita  Jich. Medical School, Dept. of Medicine, Assistant Professor, 医学部, 助手 (90306150)
高徳 正昭  自治医科大学, 医学部, 助手 (20285787)
清水 律子  自治医科大学, 医学部, 助手 (40226262)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 1999: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1998: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1997: ¥4,600,000 (Direct Cost: ¥4,600,000)
Keywordserythropoietin / transgenic mice / erythroid differentiation / UT-7 / GATA-1 / megakaryocytic differentiation / STAT 3 / STAT 1 / エリスロポエチン / トロンボポエチン / MAPキナーゼ / STAT蛋白 / チロシンキナーゼ / 細胞周期 / p21 / WAF-1 / 顆粒球・マクロファージコロニー刺激因子
Research Abstract

In this project, we clarified several things as follows;
1.Stat1 and Stat3 are activated by erythropoietin (EPO) and function as negative regulators in EPO-induced erythroid differentiation (JBC 272: 16507, 1997; Blood 92: 462, 1998).
2.Tyrosine kinases Fes and JAK2 activates Stat1 and Stat3 (manuscript in preparation).
3.Stat3 is involved in recovery from myelosupression in erythropoiesis and megakaryopoiesis (manuscript in preparation).
4. Stat3 has a negative effect on thrombopoietin (TPO)-induced megakaryocytic differentiation (manuscript in preparation.).
5. There is a crosstalk between EPO and TPO signaling pathways (manuscript in preparation).
6. Mitogen-activated protein kinases, Erk-1 and Erk-2 functions as a possible key factor for cell fate determination toward erythroid and megakaryocytic lineages (Int. Hematol., in press).
6. EPO receptor and GATA-1 are highly expressed in erythroleukemia cells (Exp. Hematol. 26: 1148, 1998).
7. FKHRL1 is one of downstream target molecules of PI3K-Akt activation pathway in EPO signal transduction (Blood in press).

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (65 results)

All Other

All Publications (65 results)

  • [Publications] Baiocchi, M., et al: "Human immunology virus(HIV)-resistant CD4+UT-7 megakaryocytic human cell line becomes highly HIV-1 and HIV-2 upon CXCR4 transfection:"Blood. 89. 2670-2678 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hoshi, S., et al: "Megakaryocyto-poietic activity of a truncated varient of mouse thrombopoletin"Biochm. Biophys. Res. Commun. 231. 823-826 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kikuchi, J., et al: "Polyploidization and functional mutation are two distinct processes during megakaryocytic differentiation involvement of cyclin-dependent kinase inhibitor p21 in polyplaidization"Blood. 89. 3980-3990 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kirito, K., et al: "A distinct function of STAT proteins in EPO signal transduction"J. Biol. Chem. 272. 16507-16513 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Komatsu, N., et al: "Cell-cycle-dependent regulation of erythropoietin receptor gene"Blood. 89. 1182-1188 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Komatsu, N., et al: "In vitro development of erythroid and megakaryocytic cells from a UT-7 subline, UT-7/GM"Blood. 89. 4021-4033 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kunitama, M., et al: "Protein kinase C and c-mycgene activation pathways in thrombopoietin signal transduction"Biochem. Biophys. Res. Commun.. 231. 290-294 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Murate, T., et al: "The production of inhibitors of metalloproteinases(TIMPs) in megakaryopoiesis: possible role of platelet- and megakaryocyte-derived TIMPs in bone marrow fibrosis"Bri. J. Heamatol.. 99. 181-189 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takatoku, M., et al: "Identification of functional domains of the human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells"J. Biol. Chem. 272. 211-216 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamashita, Y., et al: "Tec protein-tyrosine kinase is involved in the thrombopoietin/c-Mpl signaling pathway"Exp. hematol. 25. 211-216 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kirito, K., et al: "A novel function of Stat1a and Stat 3 in erythropoietin-induced erythroid differentiation of a human leukemia cell line."Blood. 92. 462-471 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Komatsu N., et al: "GATA-1 and erythropoietin receptor genes are highly expressed in erythroleukemia"Exp. Hematol.. 26. 1148-1154 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Broudy, V.C., et al: "Analysis of c-kit receptor dimerization by fluorescence energy transfer"Blood. 91. 898-906 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miura, T., et al: "Regulation of both erythroid and megakaryocytic differentiation of a human leukemia cell line"Acta Haematol.. 180-184 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada, M., et al: "Thrombopoietin supports in vitro erythroid differentiation in a human leukemia cell line"Cell Growth and Differentiation. 9. 487-496 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamashita, Y., et al: "Tec and Jak2 kineses Cooperate to Mediate Cytokine-Driven Activation of c-fos Transcription"Blood. 91. 1496-1507 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwahana, H., et al: "Different prompter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells"Eur. J. Biochem. 264. 397-406 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Komatsu N., et al: "Process from production to destruction of erythrocytes and causes of anemia"Asian Med. J.. 42. 114-121 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Madiowa S., et al: "Developmental expression of plasminogen activator inhibitor-1 associated with thrombopoietin-dependent megakaryocytic differentiation"Blood. 94. 475-482 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimizu R., et al: "A dominant negative effect of a truncated erythropoietin receptor on erythropoietin-induced erythroid differentiation"Exp. Haematol.. 27. 229-233 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Baiocchi, M.,et al.: "Human immunodeficiency virus (HIV) - resistant CD4+UT-7 megakaryocytic human cell line becomes highly HlV-1 and HIV-2 susceptible upon CXCR4 transfection: induction of cell differentiation by HIV- 1 infection."Blood. 89. 2670-2678 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hoshi,S., et al.: "Megakaryocyto- poietic activity of a truncated varient of mouse thrombopoietin."Biochem. Biophys. Res. Commun. 231. 823-826 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kikuchi, J., et al: "Polyploidization and functional mutation are two distinct processes during megakaryocytic differentiation: involvement of cyclin- dependent kinase inhibitor p21 in polyploidization."Blood. 89. 3980-3990 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kirito,K.,et al: "A distinct function of STAT proteins in EPO signal transduction."J.Biol.Chem.. 272. 16507-16513 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Komatsu,N.,et al: "Cell-cycle-dependent regulation of erythropoietin receptor gene."Blood. 89. 1182-1188 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Komatsu, N.,et al: "In vitro development of erythroid and megakaryocytic cells from a UT-7 subline, UT-7/GM."Blood. 89. 4021-4033 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kunitama,M.,et al: "Protein kinase C and c-myc gene activation pathways in thrombopoietin signal transduction."Biochem. Biophys. Res. Commun.. 231. 290-294 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Murate,T., et al: "The production of tissue inhibitors of metalloproteinases (TIMPs) in megakaryopoiesis: possible role of platelet-and megakaryocyte-derived TIMPs in bone marrow fibrosis."Bri.J.Haematol. 99. 181-189 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takatoku,M.,et al: "Identification of functional domains of the human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells."J. Biol.Chem.. 272. 7259-7263 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamashita,Y.,et al: "Tec protein-tyrosine kinase is involved in the thrombopoietin/c-Mpl signaling pathway."Exp.Hematol.. 25. 211-216 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kirito,K.,et al: "A novel function of Stat1 α and Stat3 in the erythropoietin-induced erythroid differentiation of a human leukemia cell line."blood.. 92. 462-471 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Komatsu,N., et al: "GATA-1 and erythropoietin receptor genes are highly expressed in erythroleukemia."Exp. Hematol.. 26. 1148-1154 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Broudy,V. et al.: "Analysis of c-kit receptor dimerization by fluorescence energy transfer."Blood. 91. 898-906 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miura, Y.: "Regulation of both erythroid and megakaryocytic differentiation of a human leukemia cell line, UT-7."Acta Haematol.. 180-184 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada,M.: "Thrombopoietin supports in vitro erythroid differentiation in a human leukemia cell line."Cell Growth and Differentiation. 9. 487-496 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamashita,Y.: "Tec and Jak2 Kinases Cooperate to Mediate Cytokine-Driven Activation of c-fos Transcription."Blood. 91. 1496-1507 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwahana,H.: "Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells."Eur J Biochem. 264. 397-406 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Komatsu,N.: "Process from production to destruction of erythrocytes and causes of anemia."Asian Med J. 42. 114-121 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Madoiwa,S.: "Developmental expression of plasminogen activator inhibitor-1 associated with thrombopoietin-dependent megakaryocytic differentiation."Blood. 94. 475-482 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimizu,R.: "A dominant negative effect of a truncated erythropoietin receptor on erythropoietin-induced erythroid differentiation: Possible involvement of EPOR-T in ineffective erythropoiesis of myelodyaplastic syndrome."Exp Hematol. 27. 229-233 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimizu, R.: "A dominant negative effect of a truncated erythropoietin receptor on erythropoietin-induced erythroid differentiation"Exp Hematol. 27. 229-233 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Madoiwa, S.: "Developmental expression of plasminogen activator inhibitor-1 associated with thrombopoietin-dependent megakaryocytic differentiation"Blood. 94. 475-482 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Komatsu, N.: "Process from production to destruction of erythrocytes and causes of anemia"Asian Med J. 42. 114-121 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kusano E: "Human recombinant erythoropoietin inhibits interleukin-1beta-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells"Nephrol Dial Transplant. 14. 597-603 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tominaga, S.: "Presence and expression of a novel variant form of ST2 geneproduct in human leukemic cell line UT-7/GM"Biochem Biophs Res Commun. 264. 14-18 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwahana, H.: "Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells"Eur J Biochem. 264. 397-406 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akimoto, T.: "The effect of erythropoietin on interleukin-1beta mediated increase in nitric oxide synthesis in vascular smooth muscle cells"J Hypertens. 17(in press). 1249-1256 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kuroiwa, K.: "Construction of ELISA system to quantify human ST2 protein in sera of patients. Hybridoma"Hybridoma. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kashii, Y.: "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. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Uchida, M.: "A functional role of mitogen-activated protein kinaze, Erk1 and Erk2, in the differentiation of a human leukemia cell line UT-7/GM:"Int Haematol. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kiroto K.: "A novel function of Stat3 and Stat3 in the erythropoietin-induced erythroid differentiation of a human leukemio cell line." Blood. 92. 462-417 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Broudy VC: "Analysis of c-kit receptor dimerization by fluorescence energy transfer." Blood. 91. 898-906 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamashita Y: "Tec and Jak2 kinases Cooperate to mediate Cytokine-Driven Activation of c-fos Transcription." Blood. 91. 1496-1507 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamada M:"TPO supports in vitro erythroid differentiation in a human leukemia cell line." Cell Growth and Differentiation. 9. 487-496 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miura Y: "Regulation of both erythroid and megakaryocytic differentiation of a human leukemia cell line,UT-7." Acta Haematol. 99. 180-184 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Komatsu N: "GATA-1 and erythropoietin receptor genes are highly expressed in erythroleukemia." Exp.Hematol.26. 1148-1154 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 小松則夫: "赤血球" 医学書院, 16 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Komatsu,N., et al: "Cell-cycle-dependent regulationof erythropoietin receptor gene." Blood. 89. 1182-1188 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takatoku,M., et al: "Identification of functiojnal domains of the human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells." J.Biol.Chem.272. 7259-7263 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kunitama,M., et al: "Protein kinase C and c-myc gene activation pathways in thrombopoietin signal transduction." Biochem.Biophys.Res.Commun.231. 290-294 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Komatsu,N., et al: "In vitro development of erythroid and megakaryocytic cells from a UT-7 subline,UT-7/GM." Blood. 89. 4021-4033 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kirito,K., et al: "A distinct function of STAT proteins in EPO signal transduction." J.Biol.Chem.272. 16507-16513 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Komatsu,N., et al: "GATA-1 and erythropoietin receptor genes are highly expressed in erythroleukemia." Exp.Hematol.,in press.

    • Related Report
      1997 Annual Research Report
  • [Publications] 小松則夫: "血球分化とSTAT蛋白" 最新医学社, 7 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小松則夫: "トロンボポエチンのシグナル伝達" 先端医学社, 7 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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