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Lnk and Lnk-family adaptor proteins in lymphocyte development.

Research Project

Project/Area Number 11670315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionThe University of Tokyo

Principal Investigator

TAKAKI Satoshi  The University of Tokyo, the Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (10242116)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsadaptor protein / Lnk / B cell / signal transduction / tyrosine kinase / c-Kit / hematopoiesis / アダプター蛋白質 / B細胞分化 / リンパ球分化 / APS
Research Abstract

Lnk is an adaptor protein that appears to be involved in signal transduction in lymphocytes, based on its expression in T cells and B cells and possible interaction with Grb2, PLCγ and PI3K.To illuminate the importance of Lnk in signal transduction, we generated Lnk-deficient mice. Animals lacking Lnk expression did not show any overt developmental abnormalities and were normal in size, activity, and fertility. Whereas T-cell development in the thymus was not affected, pre-B cells and immature B cells accumulated in the spleens of Lnk-/-mice. In the bone marrow, a significant expansion of the pro-B cell fraction leading to a proportionate increase in the representation of more mature B-cell precursors was observed. This increase in B-cell precursors resulted from enhanced proliferation, due to intrinsic defects within B cell precursors as demonstrated by bone marrow transfer experiments. Proliferative responses mediated by c-Kit were augmented in the Lnk-/-immature bone marrow cells. Our results suggest a specific, cell-autonomous function of Lnk in limiting B-lymphopoiesis. Further characterization of Lnk-/-mice also revealed that the full length Lnk protein is nearly twice the size of the previously published protein. Full length Lnk contains a proline-rich region followed by a PH domain, an SH2 domain, and a conserved motif harboring a candidate tyrosine phosphorylation site. Lnk is a representative of a multigene family whose members presumably function as a negative regulator of signaling mediated by tyrosine kinases.
We tried to identify another member of the adaptor protein family and isolated the mouse APS.APS is expressed in brain, kidney, muscle, and in B cells in spleen. APS is tyrosine phosphorylated at the C-terminal phosphorylation site by crosslinking of sIgM of B cells. APS is likely to play a role in signaling in B cells.

Report

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

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Takaki,S.: "Control of B cell production by the adaptor protein Lnk : definition of a conserved family of signal-modulating proteins."Immunity. 13. 599-609 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iseki,M.: "Molecular cloning of the mouse APS as a member of the Lnk family adaptor proteins."Biochem.Biophys.Res.Commun.. 272. 45-54 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Moon,B.G.: "Functional dissection of the cytoplasmic subregions of the IL-5R α chain in growth and IgG1 switch recombination of B cells."Immunology. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kouro,T.: "Bruton's tyrosine kinase (BTK) is required for signaling the CD79b-mediated pro-B to pre-B cell transition."Int.Immunol.. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takaki S.Sauer K, Iritani BM, Chien S, Ebihara Y, Tsuji K, Takatsu K, Perlmutter RM.: "Control of B cell production by the adaptor protein Lnk : definition of a conserved family of signal-modulating proteins."Immunity. 13. 599-609 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iseki M, Takaki S, Takatsu K.: "Molecular cloning of the mouse APS as a member of the Lnk family adaptor proteins."Biochem.Biophys.Res.Commun.. 272. 45-54 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kouro T, Nagata., Takaki S, Nisitani S, Hirano M, Wahl MI, Witte OW, Karasuyama H,Takatsu K.: "Bruton's tyrosine kinase (BTK) is required for signaling the CD79b-mediated pro-B to pre-B cell transition."Int.Immunol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Moon BG, Yoshida T, Shiiba M, Nakao K, Katsuki M, Takaki S, Takatsu K.: "Functional dissection of the cytoplasmic subregions of the IL-5R α chain in growth and IgG1 switch recombination of B cells."Immunology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takaki,S.: "Control of B cell production by the adaptor protein Lnk : definition of a conserved family of signal-modulating proteins."Immunity. 13. 599-609 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iseki,M.: "Molecular cloning of the mouse APS as a member of the Lnk family adaptor proteins."Biochem.Biophys.Res.Commun.. 272. 45-54 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Moon,B.G.: "Functional dissection of the cytoplasmic subregions of the IL-5R α chain in growth and IgG1 switch recombination of B cells."Immunology. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Kouro,T.: "Bruton's tyrosine kinase (BTK) is required for signaling the CD79b-mediated pro-B to pre-B cell transition."Int.Immunol.. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Naito, A.: "Severe osteopetrosis, defective interleukin-I signalling and lymph node organogenesis in TRAF6-deficient mice"Genes to Cells. 4. 353-362 (1999)

    • Related Report
      1999 Annual Research Report

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

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