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1999 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 1997 – 1999
Keywordserythropoietin / transgenic mice / erythroid differentiation / UT-7 / GATA-1 / megakaryocytic differentiation / STAT 3 / STAT 1
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).

  • Research Products

    (40 results)

All Other

All Publications (40 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2001-10-23  

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