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Analysis of mechanisms that regulate differentiation of erythroid and megakaryocyte

Research Project

Project/Area Number 11680713
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionRIKEN Institute

Principal Investigator

NAGATA Yuka  RIKEN Institute, INVESTIGATOR, 分子細胞生物学研究室, 協力研究員 (40281620)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordserythroid / megakaryocyte / erythropoetin / thrombopoetin / MAPK / G protein signal pathway / RGS protein / SDF-1 / 赤芽球 / エリストロポエチン / JNK / p38
Research Abstract

JNK and p38 subgroups of MAP kinases have been suggested to play a critical role in apoptosis, cell growth and/or differentiation. I found that short cellular stresses, inducing transient activation of JNK and p38, lead to erythroid differentiation rather than apoptosis. Furthermore, activation of JNK and p38 is required for both cell differentiation and apoptosis, and the duration of their activation may determine the cell fate, cell differentiation and apoptosis.
Hematopoietic progenitor kinase-1 (HPK1), which is expressed predominantly in hematopoietic cells, leads to activation of JNK in nonhematopoietic cells. Upstream activators of HPK1 currently remain elusive and its precise role in hematopoiesis has yet to be defined. I therefore examined the possible involvement of HPK1 in erythropoetin (Epo) and environmental stress-induced JNK activation. I found that Epo induces activation of both HPK1 and HS1 while cellular stresses activate only HS1, and that the HPK1-JNK pathway is invol … More ved in Epo-induced growth and differentiation signals.
The regulator of G protein signaling (RGS) negatively regulates the α subunit of G proteins by accelerating their intrinsic GTPase activity. Here I report the isolation and characterization of a novel mouse RGS, termed RGS18. RGS18 mRNA was predominantly detected in spleen and hematopoietic cells, and immunohistochemical studies demonstrated that RGS18 was expressed in megakaryocytes, platelets, granulocytes/monocytes and weakly in hematopoietic stem cells, but not in lymphocytes and erythrocytes. While various subcellular localization of RGS has been reported, RGS18 was found to be localized in cytoplasm in megakaryocytes. In vitro binding assays of RGS18 demonstrated that RGSl8 specifically binds to two α subunits of the G protein, Gαi and Gαq. Furthermore, RGS18 clearly exhibited GAP activity for Gαi and Gαq but not for Gαs or Gα12. In addition, a chemokine SDF-1, which has been reported to stimulate megakaryocyte colony formation in the presence of thrombopoietin, affected the binding of RGS18 to Gαi but not to Gαq. Therefore, the newly isolated RGS18 may play an important role in proliferation, differentiation and/or migration of megakaryocytes. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Nagata,Y., et al.: "A novel regulator of G-protein signaling bearing GAP activity for Gαi and Gαq in megakaryocytes."Blood. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagata,Y., et al.: "Requirement of activation of JNK and p38 for environmental stress-induced erythroid differentiation and apoptosis and of inhibition of ERK for apoptosis."Blood. 94(3). 853-863 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagata,Y., et al.: "Activation of hematopoietic progenitor kinase-1 by erythropoietin."Blood. 93(10). 3347-3354 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 永田由香 ほか: "血液・腫瘍科「MAPKとアポトーシス」"科学評論社. 7 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 永田由香 ほか: "分子細胞治療「赤血球/巨核球の分化制御シグナル」"先端医学社(印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 永田由香: "生体の科学「ノックアウトマウスリスト;神経系転写因子制御因子」"金原一郎記念医学医療振興財団/医学書院. 2 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagata, Y., Oda, M., Nakata, H., Shozaki, Y., Kozasa, T., and Todokoro, K.: "A novel regulator of G-protein signaling bearing GAP activity for Gαi and Gαq in megakaryocytes."Blood. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagata, Y., and Todokoro, K.: "Requirement of activation of JNK and p38 for environmental stress-induced erythroid differentiation and apoptosis and of inhibition of ERK for apoptosis."Blood. 94(3). 853-863 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagata, Y., Kiefer, F., Watanabe, T., and Todokoro, K.: "Activation of hematopoietic progenitor kinase-1 by erythropoietin."Blood. 93(10). 3347-3354 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagata, Y., and Todokoro, K.: "Differentiation signals in erythroid and megakaryocyte."Cellular Molecular Medicine. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagata, Y.: "Lists of knock out mice."Seitai no Kagaku. 51(5). 445-446 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagata, Y., and Todokoro, K.: "MAPK and apoptosis."Hematology & Oncology. 40. 315-321 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagata,Y., et al.: "A novel regulator of G-protein signaling bearing GAP activity for Gαi and Gαq in megakaryocytes."Blood. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 永田由香 ほか: "分子細胞治療「赤血球/巨核球の分化制御シグナル」(印刷中)"先端医学社. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 永田由香: "生体の科学「ノックアウトマウスリスト;神経系転写因子制御因子」"金原一郎記念医学医療振興財団/医学書院. 2 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagata Y.et al.: "Activation of hematopoietic progenitor kinase-1 by erythropoietin"Blood. 93(10). 3347-3354 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagata Y.et al.: "Requirement of activation of JNK and p38 for environmental stress-induced Erythroid differentiation and apoptosis and of inhibition of ERK for apoptosis"Blood. 94(3). 853-863 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 永田由香ほか: "血液・腫瘍科"科学評論社(発表予定). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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