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Mechanism of platelet production

Research Project

Project/Area Number 09480200
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

TODOKORO Kazuo  RIKEN,Molecular Cell Science Lab, Scientist, 分子細胞生物学研究室, 副主任研究員 (80172170)

Co-Investigator(Kenkyū-buntansha) KOTANI Shuji  RIKEN,Molecular Cell Science Lab, Postdoc.Scientist, 分子細胞生物学研究室, 基礎科学特別研究員 (60281622)
NAGATA Yuka  RIKEN,Molecular Cell Science Lab, Postdoc.Scientist, 分子細胞生物学研究室, 基礎科学特別研究員 (40281620)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 1998: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1997: ¥10,300,000 (Direct Cost: ¥10,300,000)
KeywordsMegakaryocytes / Platelets / 巨核球
Research Abstract

Molecular mechanism of platelet production still remains unclear. Therefore, we investigated the mechanism of megakaryocyte maturation processes, thrombopoietin (Tpo)-induced polyploidization of megakaryocytes, proplatelet formation of matured megakaryocytes, and Tpo-induced differentiation signal transduction. It has been described that polyploidization of megakaryocytes is due to DNA replication without mitosis, but we found that Tpo-induced primary megakaryocytes from bone marrows undergo polyploidization through unusual mitotic process. Mekagaryocytes go into mitosis until anaphase A, but at this stage the sister chromatids Would not go far apart enough to be separated nuclei. As for proplatelet formation, we found a factor in thrombocytopenic patients which stimulates proplatelet formation of mouse primary megakaryocytes in vitro. We are trying to isolate this factor by various chromatographic techniques. We also found that proplatelets were not produced from the megakaryocytes of NFE-2 knock-out mice. Thus we attempted to isolate a factor which is not expressed in NFE-2 knock-out mice, and a number of interesting factors were isolated. We are investigating the biological functions of these new factors.

Report

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

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Y.Nagata et al.: "Serun thrombopoietin level is not resulated by trausumption but the total counts of both megakauyo as tes and plaletets" Thrombosis & Haemostasis. 77. 808-814 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Nagata et al.: "Thrombopoietin-indned polyploidization of bone marrons megakaryocytes is dveto unyne negulatory mech of mitosis" Journal of Cell Biology. 139. 449-457 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Nagata et al.: "Regulation of megakauyocy topaesis by thrsmbopoieter and stromal cells" Leukemia. 11. 435-438 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hamazaki et al.: "Tec is inuolved in H-Drotein coupled receptor-and integrin-gignals in human blood platelets" Oncogene. 16. 2773-2779 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Nagata et al.: "Activation of TNK signaling pathway by enythropoeth thromboioietin and interbukin 3" BLOOD. 89. 2664-2669 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Nagata et al.: "Activation of heruatopoietic progenitors kinare-1 by enythropoietin" BLOOD. 印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Nagata et al.: "Activation of p38 MAD kinare ciscade by enythropsethr and interlenkin 3" BLOOD. 90. 929-934 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Reese,et al.: "Epo-indued hempglobiaisatos of SKT6 cells is mediated by minimal cytoplanmic dgmain of Eps seaptor" Growth Factors. 14. 161-176 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] ER.Sharlow et al.: "Hematopoetic cell phosphatase negatively regulates Epo-indunced hemoslolyization" BLOOD. 90. 2175-2187 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Kotani et al.: "PKA and polo-like kinase regulates anaplrace-mowoting complex activity and mitosis prognossion" Molecular Cell. 1. 371-380 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] RC.Gregory et al.: "Enyhropooctin receptor and STA5-speisfoc pathway promotes SKT6 cell hemoslobinization" BLOOD. 1. 1104-1118 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Nagata et al.: "Activation of p38 MAD kinre and JNK but not ERK is negvied for enythnopoetin-indussc differeatiation" BLOOD. 92. 1859-1869 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Kojima et al.: "Immature unegakaryocytes undergo apotosis in the absence of thronbopoietin" Experimental Hematology. 27. 131-138 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagata, Y., Shozaki, Y., Nagahisa, H., Nagasawa, T., Abe, T.& Todokoro, K.: "Serum thrombopoietin level is not regulated by transcription but by the total counts of both megakaryocytes and platelets during thrombocytopenia and thrombocytosis." Thromb.Haemost.77. 808-814 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagata, Y., Muro, Y.& Todokoro, K.: "Thrombopooietin-induced polyploidization of bone marrow megakaryocytes is due to unique regulatory mechanism of late mitosis." J.Cell Biol.139. 449-457 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagata, Y., Nagshisa, H., Nagasawa, T.& Todokoro, K.: "Regulation of megakaryocytopoiesis by thrombopoietin and stromal cells." Leukemia. 11. 435-438 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagata, Y., Nishida, E.& Todokoro, K.: "Activation of JNK signaling pathway by erythropoietin, thrombopoietin and interleukin-3." Blood. 89. 2664-2669 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagata, Y., Moriguchi, M., Nishida, E.& Todokoro, K.: "Activation of p38 MAP kinase cascade by erythropoietin and interleukin-3" Blood. 90. 929-934 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Reese, TT., Gregory, RC., Sharlow, ER., Pacifici, R., Crouse, J.A., Todokoro, K.& Wojchowski, DM: "Epo-induced hemoglobinization of SKT6 cells is mediated by minimal cytoplasmic domains of the Epo or prolactin receptors without modulation of GATA-1 or EKLF." Growth Factors. 14. 161-176 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sharlow, ER., Pacifici, R., Crouse, J., Batac, J., Todokoro, K.& Wojchowski, DM.: "Hematopoietic cell phosphatase negatively regulates Epo-induced homoglobinization in erythroleukemic SKT6 cells." Blood. 90. 2175-2187 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hamazaki, Y., Kojima, H., Mano, H., Nagata, Y., Todokoro, K., Abe, T.& Nagasawa, T.: "Tec is involved in G protein-coupled receptor-and integrin-mediated signalings in human blood platelets." Oncogene. 16. 2773-2779 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kotani, S., Tugendreich, S., Fujii, M., Jorgensen, P-M., Watanabe, N., Hoog, C., Hieter, P.& Todokoro, K.: "PKA and MPF-activated polo-like kinase regulate anaphase-promoting complex activity and mitosis progression." Molecular Cell. 1. 371-380 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Gregory, R.C., Jiang, N., Todokoro, K., Crouse, J., Pacifici, R.E.& Wojchowski, D.M.: "Erythropoietin receptor and STAT5-specific pathways promote SKT6 cell hemoglobinization." Blood. 92. 1104-1118 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagata, Y., Takahashi, N., Davis, R.& Todokoro, K.: "Activation of p38 MAP kinase and JNK but not ERK is required for erythropoietin-induced erythroid differentiation." Blood. 92. 1859-1869 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osada, M., Komeno, T., Todokoro, K., Takizawa, M., Kojima, H., Suzukawa, K., Ninomiya, H., Tsukasa, A.& Nagasawa, T.: "Immature megakaryocytes undergo apoptosis in the absence of thrombopoietin." Exp.Hematol.27. 131-138 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagata, Y., Kiefer, F., Watanabe, T.& Todokoro, K.: "Activation of hematopoietic progenitor kinase-1 by erythropoietin." Blood. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 永田由香ら: "Requirement of activation of JNK and p38 for environmental stress-induced differentiation and of inaothieform of ERIC for apoptosis" BLOOD. (印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 浜崎洋子ら: "Tec is involved in G probein coupled-reaptor-and integrin-mediated signdsing in human blood platclets" Encogene. 16. 2773-2779 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 長田 雅樹ら: "Immature megakanyo agles undugo apoptosis in the absem of thaombopoietin" Experimental Heuratology. 27. 131-138 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 永田由香ら: "巨核球の多倍体化を捉えた" 蛋白質核酸酵素. 42. 1388-1388 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Nagata et al: "Activation of JNK signaling parhway by elythupmetin TPO & IL3" BLOOD. 89. 2664-2669 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Kimura et al: "Cell cycle-dependent expression & spindle pole localigatm at a novel human moteun kinare AlK" Journal of Biological Chemistry. 272. 13766-13771 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Nagata et al: "Serunr TPO lcuel is not regulated by transcuption but by the total count of both megakaugocutes & platelets" Thrombosis & Haemostasis. 77. 808-814 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Nagata et al: "Activation of p38 MAP kinase by Epo & IL3" BLOOD. 90. 929-934 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] TT.Reese et al: "Epo-induced hemoglobinization of SFTb alls is meclioled by mininal cytrplasmic domain of Epo receptn" Growth Factors. 14. 161-176 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] ER.Sharlow et al: "Hematoporetic all phophatase negatively reprtate Epoinduced henuglobinigation of sRTb cells" BLOOD. 90. 2175-2187 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Nagata et al: "Thurpopuietin-incheed polyplordzation of bone wanrs megahauyocgtes is due to unicue segalatry macheimn" Journal of Cell Biology. 139. 449-457 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Kotani et al: "PKA and MPF-activated polo-tihe kinare repulate APC and mitosis megversion" Mole cular Cell. 1. 371-380 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Hamazaki et al: "Tec is involved in G protain-coupled reuptn-and integrin-mediated signaling" Onwgeue. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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

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