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Roles of serine phosphorylation of thrombopoietin receptor

Research Project

Project/Area Number 13671085
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKeio University

Principal Investigator

MIYAKAWA Yoshitaka  Keio University, School of Medicine, Assistant professor, 医学部, 専任講師 (50250238)

Co-Investigator(Kenkyū-buntansha) KIZAKI Masahiro  Keio University, School of Medicine, Associate professor, 医学部, 専任講師 (20161432)
IKEA Yasuo  Keio University, School of Medicine, 医学部, 教授 (00110883)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsthrombopoietin / megakaryocyte / Phosphorylation / hematopoiesis / セリン残基 / レセプター
Research Abstract

c-Mpl is a cognate receptor for a cytokine, thrombopoietin, which regulates Megakaryopoiesis and thrombopoieis in vivo. Thrombopoietin induces the activation of Jak2, Tyk2, PI3 kinase, MAP kinase in Mpl-expressing cell lines and normal megakaryocytes. When the serine residues of Mpl were altered with alanine, the proliferation of BaF3 cells expressing those mutants were suppressed compared to the wild type Mpl. The serine residues were constitutively phosphorylated and its phosphorylation was enhanced after stimulation with thrombopoietin. We also confirmed the expression of GFP protein in primary megakaryocytes using retrovirus, and this system should be useful to analyze the function of Mpl mutants in primary cells. The promoter region of thrombopoietin was analyzed by reporter assays. We found retinoic acid regulates the transcription of thrombopoietin gene.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Kizaki M et al.: "Long-term administration of PEG-MGDF dramatically improved cytopenias in a patient with myelodysplastic syndrome"Br J Haematol. 122. 764-767 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kinjo K et al.: "All-trans retinoic acid directly upregulates thrombopoietin transcription in human bone marrow stromal cells"Exp Hematol. 32. 45-51 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kizaki M et al.: "Long-term administration of PEG-MGDF dramatically improved cytopenias in a patient with myelodysplastic syndrome."Br J Haematol. 122. 764-767 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kinjo K et al.: "All trans retinoic acid directly upregulates thrombopoietin transcription in human bone marrow stromal cells"Exp Hematol. 32. 45-51 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kizaki M et al.: "Long-term administration of pegylated recombinant human megakaryocyte growth and development factor dramatically improved cytopenias in a patient with myelodysplastic syndrome"Br J Haematol. 122. 764-767 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kinjo K et al.: "All-trans retinoic acid directly up-regulates thrombopoietin transcription in human bone marrow stromal cells."Exp Hematol. 32. 45-51 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kohmura K et al.: "Different roles of p38 MAPK and ERK in STI571-induced multi-lineage differentiation of K562 cells."J Cell Physiol. 198. 370-376 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Drachman JG et al.: "MpI/Jak2 chimeric receptors : Both Jak2 and the membrane proximal domain of Mpl are required for cellular proliferation"J Biol Chem. 227. 23544-23553 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Awaya N et al.: "Novel variant isoform of G-CSF receptor involved in induction of proliferation of FDCP-2 cells : Relevance to the pathogenesis of myelodysplastic syndrome"J Cell Physiol. 191. 327-335 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sewafuji K et al.: "Cyclosporin A induces erythroid differentiation of K562 cells through p38 MAPK and ERK pathways"Am J Hematol. 72. 67-69 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 宮川義隆, 池田康夫: "Annual review血液2002"中外医薬社. 245 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 宮川義隆: "細胞の形態形成の基本メカニズム"金芳堂. 200 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 宮川義隆: "Annual review 2002 血液"中外医薬社. 248 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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