• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2002 Fiscal Year Final Research Report Summary

Regulation of signal transduction for cell growth and differentiation by Lnk-family adaptor proteins

Research Project

Project/Area Number 13470069
Research Category

Grant-in-Aid for Scientific Research (B)

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)

Co-Investigator(Kenkyū-buntansha) KARIYONE Ai  The University of Tokyo, The Institute of Medical Science, Teaching Staff, 医科学研究所, 教務職員 (50114450)
Project Period (FY) 2001 – 2002
Keywordsimmunology / cell growth / signal transduction / adaptor protein / regenerative medicine / bone marrow transfer / B lymphocyte / hematopoietic stem cell
Research Abstract

Lnk is an adaptor protein expressed mainly in lymphocytes. Lnk forms part of an adaptor protein family together with APS and SH2-B, whose members share the presence of a homologous N-terminal domain with putative proline-rich protein interaction motifs, followed by PH and SH2 domains, and a conserved C-terminal tyrosine phosphorylation site.
Lnk regulates B cell production by negatively controlling pro-B cell expansion. Lnk-deficient mice show enhanced B cell production due to the hypersensitivity of B cell precursors to SCF, a c-Kit ligand. In addition, the numbers of hematopoietic progenitors in the bone marrow increase in lnk-deficient mice. Competitive repopulation assays demonstrate that the ability of hematopoietic progenitors to generate various lineages of hematopoietic cells is greatly enhanced by the absence of Lnk. Reduction of c-Kit expression by the introduction of the Kit^W mutation on a lnk^<-/-> background partially but significantly normalized B cell overproduction. In contrast, an enhanced ability of HSCs was not normalized, suggesting involvement of as yet unidentified mechanism(s) in addition to the enhanced c-Kit signaling. Lymphocyte production was impaired in a dose dependent manner upon overexpression of Lnk in lymphoid cells by transgenic approach. Lnk regulates lymphopoiesis and mature B cell subpopulations by regulating c-Kit-indipendent as well as c-Kit-dependent signaling pathways. Lnk is phosphorylated by and associates with c-Kit. Lnk selectively inhibits c-Kit-mediated proliferation by inhibiting tyrosine phosphorylation of Gab2 and activation of the MAPK cascade.
We also generated SH2-B-deficient mice and APS-deficient mice and investigated physiological roles of SH2-B and APS in vivo.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Takaki, S.: "Impaired Lymphopoiesis and Altered B Cell Subpopulations in Mice Overexpressing Lnk Adaptor Protein"J. Immunol.. 170・2. 703-710 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Ohtsuka: "SH2-B is Required for Both Male and Female Reproduction"Mol. Cell. Biol.. 22・9. 3066-3077 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takaki, S.: "Enhanced Hematopoiesis by Hematopoietic Progenitor Cells Lacking Intracellular Adaptor Protein, Lnk"J. Exp. Med.. 195・2. 151-160 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada, A.: "Identification and Characterization of a Transcriptional Regulator for the lck Proximal Promoter"J. Biol. Chem.. 276・21. 18082-18089 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kouro, T.: "Bruton's tyrosine kinase is required for signaling the CD79b-mediated pro-B to pre-B cell transition"Int. Immunol.. 13・4. 485-493 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Moon, B.G.: "Functional dissection of the cytoplasmic subregions of the interleukin-5 receptor alpha chain in growth and immunoglobulin G1 switch recombination of B cells"Immunology. 102・3. 289-300 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takaki S, Tezuka Y, Sauer K, Kubo C, Kwon S, Armstead E, Nakao K, Katsuki M, Perlmutter RM, Takatsu K: "Impaired lymphopoiesis and altered B cell subpopulations in mice overexpressing lnk adaptor protein"Jimmunol. 170. 703-710 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohtsuka S, Takaki S. Iseki M, Miyoshi K, Nakagata N, Kataoka Y, Yoshida N, Takatsu K, Yoshimura A: "SH2-B is required for both male and female reproduction"Mol Cell Biol. 22. 3066-3077 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takaki S, Morita H, Tezuka Y, Takatsu K: "Enhanced hematopoiesis by hematopoietic progenitor cells lacking intracellular adaptor pro tein, Lnk"J Exp Med. 195. 151-160 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada A^*, Takaki S^* (^* equally contributed authors), Hayashi F, Georgopoulos K, Perlmutter RM, Takatsu K: "Identification and characterization of a transcriptional regulator for the lck proximal promoter"J Biol Chem. 276. 18082-18089 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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 a chain in growth and IgG1 switch recombination of B cells"Immunology. 102. 289-300 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kouro T, Nagata K, Takaki S. Nisitani S, Hirano M, Wahl MI, Witte OW, Karasuyama H, Takatsu K: "Bruton's tyrosine kinase is required for signaling the CD79b-mediated pro-B to pre-B cell transition"lnt Immunol. 13. 485-493 (2001)

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

URL: 

Published: 2004-04-14  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi