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1999 Fiscal Year Final Research Report Summary

Functional analyses of roles of tyrosine kinases/phosphatases in lymhpcyte signaling

Research Project

Project/Area Number 10044288
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKobe University

Principal Investigator

MINAMI Yasuhiro  KOBE UNIVERSITY, SCHOOL OF MEDICINE, Professor, 医学部, 教授 (70229772)

Co-Investigator(Kenkyū-buntansha) KOSUGI Atsushi  Osaka University, School of Medicine, Associate Professor, 医学部, 助教授 (90186685)
OGATA Masato  Osaka University, School of Medicine, Research associate, 医学部, 助手 (60224094)
OTANI Hiroki  Shimane Medical University, Professor, 医学部, 教授 (20160533)
UMEHARA Hisanori  Osaka Dental University, Lecturer, 歯学部, 講師 (70247881)
TANAKA Yosiya  University of Occupational and Environmental Health School of Medicine, Lecturer, 医学部, 講師 (30248562)
Project Period (FY) 1998 – 1999
Keywordslymphocytes / signal transduction / protein tyrosine kinase / protein tyrosine phosphatases / adaptors / protooncogene products / cell adhesion
Research Abstract

In this study, we have found that the proto-oncogene products, H-Ras and c-Myc, act co-operatively to induce homophilic cell adhesion of lymphocytes through the induction of VLA-4 activation and of VCAM-1 expression (Minami, Tanaka). It was also shown that Syk tyrosine kinase and SHP-2 tyrosine phosphatase play important roles in IL-2-induced signal transduction (O'Shea). It was found that an adaptor molecule, LAT is palmitoylated and sequestered at GEM, and is required for the development and activation of T lymphocytes (Samelson). An importance of GEM in T cell engagement was also elucidated (Kosugi). In this study, we have established an experimental system using exo utero method, aiming to examine the effects of tyrosine kinase/phosphatase inhibitors on lymphocyte development in vivo (Otani). We have also shown that a lymphocyte-specific tyrosine phosphatase, LC-PTP, inhibits ERK that is activated during T cell activation (Ogata). It was reported that topoisomerase II inhibitors induce apoptosis of lymphocytes. In this study, it was found that Lyn tyrosine kinase regulates positively the topoisomerase II inhibitor-induced apoptosis of lymphocytes (Yamamura). We have also examined a possible role of tyrosine phosphatases in the process of lymphocyte-macrophage interaction (Moriyama). It was shown that engagement of LFA-1 and of TCR results in a synergistic tyrosine phosphorylation of Fak tyrosine kinase (Umehara). In this collaborative study, we have exchanged results mutually, and have discussed about the respective results extensively. We have also discussed to plan our future collaborative experiments.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Liu, Z-J., --, Minami, Y.: "A critical role for cyclin C in promotion of the hematopoietic cell cycle by co-operation with c-Myc"Mol. Cell Biol.. 18. 3445-3454 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Liu, Z-J., --, Minami, Y.: "Functional co-operation of cyclin C and c-Myc in mediating homotypic cell adhesion via VLA-4 activation and VCAM-1 expression"Blood. 92. 4700-4711 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Gadina, M., --, O'Shea, J.J.: "Il-2 but not Il-4 induces the phosphorylation of a 98kD protein associated with SHP-2, PI3K and Brb-2"J. Immunol.. 162. 2081-2086 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Leonard, W.J., O'Shea, J.J.: "Jaks and STATs : Biological implications"Annu. Rev. Immunol.. 16. 293-322 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sloan, L.J., --, Samelson, L.E.: "ZAP-70 association with T cell receptor zeta (TCRzeta): fluorescence imaging of dynamic changes upon cellular stimulation"J. Cell. Biol.. 143. 613-624 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhang, W., --, Samelson, L.E.: "LAT palmitoylation : its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation"Immunity. 9. 239-246 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhang, H., --, Otani, H.: "Induction of ectopic corticotropic tumor in mouse embryos by exo utero cell transplantation and its effects on the mouse fetal adrenal gland"Endocrinology. 139. 3306-3315 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogata, M., --, Hamaoka, T.: "Effects of overexpression of PTP36, a putative protein tyrosine phosphatase, on cell-adhesion, cell-growth, and cytoskeletons in Hela cells."J. Biol. Chem.. 274. 12905-12909 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogata, M., --, Hamaoka, T.: "Inactivation of mitogen-activated protein kinases by mammalian tyrosine-specific phosphatase, PTPBR7"Biochem. Biophys. Res. Commun.. 265. 52-26 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kosugi, A., --, Hamaoka, T.: "Physical and functional association between thymic shared antigen-1/stem cell antigen-2 and the T cell receptor complex"J. Biol. Chem.. 273. 12301-112306 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Liu, Z-J., --, Minami, Y.: "A novel role for H-Ras in the regulation of VLA-4 integrin and VCAM-1 via c-Myc-dependent and -independent mechanisms"J. Immunol.. 163. 4901-4908 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Gadina, M., --, O'Shea, J.J.: "Involvement of SHP-2 in multiple aspects of Il-2 signaling : Evidence for a positive regulatory role"J. Immunol.. 160. 4657-4661 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chen, E.H., --, O'Shea, J.J.: "Not just another meeting : the coming of age of JAKs and STATs"Immunol. Today. 19. 338-341 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhang, W.G., --, and Samelson, L.E.: "Essential role of LAT in T cell development"Immunity. 10. 1282-1288 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oh-hara, M., --, Ogata, M., Hamaoka, T.: "Direct suppression of TCT-mediated activation of extracellular signal-regulated kinase by leukocyte protein tyrosine phosphatase, a tyrosine-specific phosphatase"J. Immunol.. 163. 128-1288 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Osage, A., --, Jamaica, T.: "Translocation of tyrosine-phosphorylated TCRζ chain to glycolipid-enriched membrane domains upon T cell activation"Int. Immunol.. 11. 1395-1401 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maruo, A., --, Minami, Y., Yamamura, H.: "Protein tyrosine kinase Lyn mediates apoptosis induced by topoisomerase II inhibitors in DT40 cells"Int. Immunol.. 11. 1371-1380 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, Y., Minami, Y., --, Eto, S.: "H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells"J. Immunol.. 163. 6209-6216 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tabassam, F.H., Umehara, H., --, Domae, N.: "β2-integrin, LFA-1 and TCR/CD3 synergistically induce tyrosine phosphorylation of focal adhesion kinase (pp215FAK) in PHA-activated T cells"Cell Immunol.. 193. 179-184 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Minami, Y., -, Yamanura, H.: "Redox regulation of cell signaling and its clinical applications"Marcel Dekker Inc. NY, USA. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Liu,Z-J., --, and Minami,Y.: "Functional co-operation of cyclin C and c-Myc in mediating homotypic cell adhesion via VLA-4 activation and VCAM-1 expression"Blood. 92. 4700-4711 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Liu,Z-J., --, and Minami,Y.: "A novel role for H-Ras in the regulation of VLA-4 integrin and VCAM-1 via c-Myc-dependent and -independent mechanisms"J. Immunol.. 163. 4901-4908 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Leonard,W.J., and O'Shea,J.J.: "Jaks and STATs : Biological implications"Annu. Rev. Immunol.. 16. 293-322 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhang,W.G., and Samelson,L.E.: "Essential role of LAT in T cell development"Immunity. 10. 323-332 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oh-hara,M., Ogata,M., --, and Hamaoka,T.: "Direct suppression of TCR-mediated activation of extracellular signal-regulated kinase by leukocyte protein tyrosine phosphatase, a tyrosine-specific phosphatase"J. Immunol.. 163. 1282-1288 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maruo,A., --, Minami,Y., and Yamamura,H.: "Protein tyrosine kinase Lyn mediates apoptosis induced by topoisomerase II inhibitors in DT40 cells"Int. Immunol.. 11. 1371-1380 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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