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Functional analysis of Tec family kinases in normal hematopoiesis and hematological disease.

Research Project

Project/Area Number 13671081
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionJichi Medical School

Principal Investigator

YAMASHITA Yoshihiro  Jichi Medical School, Department of Medicine, Research Associate, 医学部, 助手 (10326861)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsSak kinase / Tec kinase / tyrosine phosphorylation / PEST sequence / 造血前駆細胞 / BRDG1 / ドッキング蛋白 / PHドメイン / B細胞抗原受容体(BCR) / CREB
Research Abstract

The murine sak gene encodes a putative serine-threonine kinase which is homologous to the members of the Plk/Polo family. Although Sak protein is presumed to be involved in cell growth mechanism, efforts have failed to demonstrate its kinase activity. Little has been, therefore, elucidated how Sak is regulated and how Sak contributes to cell proliferation. Tec is a cytoplasmic protein-tyrosine kinase (PTK) which becomes activated by the stimulation of cytokine receptors, lymphocyte surface antigens, heterotrimeric G protein-linked receptors, and integrins. To clarify the in vivo function of Tec, we have tried to isolate the second messengers of Tec by using the yeast two-hybrid screening. One of such Tec-binding proteins turned out to be Sak. In human kidney 293 cells, Sak became tyrosine-phosphorylated by Tec, and the serine-threonine kinase activity of Sak was detected only under the presence of Tec, suggesting Sak to be an effector molecule of Tec. In addition, Tec activity efficiently protects Sak from the "PEST" sequence-dependent proteolysis. Internal deletion of the PEST sequences led to the stabilization of Sak proteins, and expression of these mutants acted suppressive to cell growth. Our data collectively supports a novel role of Sak acting in the PTK-mediated signaling pathway.

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Yoshida, K. et al.: "Screening of genes specifically activated in the pancreatic juice ductal cells from the patients with pancreatic ductal carcinoma"Cancer Sci.. 94. 263-270 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Makishima, H. et al.: "DNA microarray analysis of T cell-type lymphoproliferative disease of granular lymphocytes"Br. J. Haematol.. 118. 462-469 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita, Y. et al.: "Sak serine/threonine kinase acts as an effector of Tec tyrosine kinase"J. Biol. Chem.. 276. 39012-39020 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokohari, K. et al.: "Isoform-Dependent Interaction of BRDG1 with Tec Kinase"Biochem. Biophys. Res. Commun.. 289. 414-420 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyazato, A. et al.: "Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematonoietic stem cell fraction"Blood. 98. 422-427 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohmine, K. et al.: "Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells"Oncogene. 20. 8249-8257 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida,K., Ueno,S., Iwao,T., Yamasaki,S., Tsuchida,A., Ohmine,K., Ohki,R., Choi,Y.,L., Koinuma,K., Wada,T., Ota,J., Yamashita,Y., Chayama,K., Sato,K., and Mano,H.: "Screening of genes specifically activated in the pancreatic juice ductal cells from the patients with pancreatic ductal carcinoma"Cancer Sci. 94. 263-270 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takenaga,M., Hatano,M., Takemori,M., Yamashita,Y., Okada,S., Kuroda,Y., and Tokuhisa,T.: "Bc16-dependent transcriptional repression by BAZF"Biochem Biophys Res Commun. 303. 600-608 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Makishima,H., Ishida,F., Ito,T., Kitano,K., Ueno,S., Ohmine,K., Yamashita,Y., Ota,J., Ota,M., Yamauchi,K., and Mano,H.: "DNA microarray analysis of T cell-type lymphoproliferative disease of granular lymphocytes"Br J Haematol. 118. 462-469 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita,Y., Kajigaya,S., Yoshida,K., Ueno,S., Ota,J., Ohmine,K., Ueda,M., Miyazato,A., Ohya,K., Kitamura,T., Ozawa,K., and Namo,H.: "Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase"J Biol Chem. 276. 39012-39020 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokohari,K., Yamashita,Y., Okada,S., Ohya,K., Oda,S., Hatano,M., Mano,H., Hirasawa,H., and Tokuhida,T.: "Isoform-dependent interaction of BRDG1 with Tec kinase"Biochem Biophys Res Commun. 289. 414-420 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohmine,K., Ota,J., Ueda,M., Ueno,S., Yoshida,K., Yamashita,Y., Kirito,K., Imagawa,S., Nakamura,Y., Saito,K., Akutsu,M., Mitani,K., Kano,Y., Komatsu,N., Ozawa,K., and Mano,H.: "Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells"Oncogene. 20. 8249-8257 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyazato,A., Ueno,S., Ohmine,K., Ueda,M., Yoshida,K., Yamashita,Y., Kaneko,T., Mori,M., Kirito,K., Toshima,M., Nakamura,Y., Saito,K., Kano,Y., Furusawa,S., Ozawa,K., and Mano,H.: "Identification of myelodysplastic syndrome-speicific genes by DNA microarray analysis with purified hematopoietic stem cell fraction"Blood. 98. 422-427 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Makishima, H. et al.: "DNA microarray analysis of T cell-type Iymphoproliferative disease of granular lymphocytes"Br. J. Haematol.. 118. 462-469 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita, Y. et al.: "Sak serine/threonine kinase acts as an effector of Tec tyrosine kinase"J. Biol. Chem.. 276. 39012-39020 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yokohari, K. et al.: "Isoform-Dependent Interaction of BRDG1 with Tec Kinase"Biochem. Biophys. Res. Commun.. 289. 414-420 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyazato, A. et al.: "Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cells"Blood. 98. 422-427 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohmine, K. et al.: "Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cell fraction"Oncogene. 20. 8249-8257 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita, Y. et al.: "Sak serine/threonine kinase acts as an effector of Tec tyrosine kinase"J. Biol. Chem.. 276. 39012-39020 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yokohari, K. et al.: "Isoform-Dependent Interaction of BRDG1 with Tec Kinase"Biochem. Biophys. Res. Commun.. 289. 414-420 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyazato, A. et al.: "Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction"Blood. 98. 422-427 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohmine, K. et al.: "Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells"Oncogene. 20. 8249-8257 (2001)

    • Related Report
      2001 Annual Research Report

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

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