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1998 Fiscal Year Final Research Report Summary

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
KeywordsMegakaryocytes / Platelets
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.

  • Research Products

    (26 results)

All Other

All Publications (26 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-12-08  

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