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Molecular analysis of BCR signaling pathways

Research Project

Project/Area Number 11694325
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKansai Medical University

Principal Investigator

KUROSAKI Tomohiro  Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (50178125)

Co-Investigator(Kenkyū-buntansha) INABE Kazunori  Kansai Medical University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (30309215)
石合 正道  関西医科大学, 医学部, 助手 (90298844)
前田 明人  関西医科大学, 医学部, 講師 (50298882)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsBCR / BLNK / Bam 32 / BLC-γ2 / calcium
Research Abstract

Drs. Chan and Kurosaki have coworked the molecular mechanisms by which BLNK, an adaptor molecule, participates in BCR signaling pathways. Using reconstitution studies, we found that SLP-76, BLNK-related adaptor molecule expressed in T cells, canhot reconstitute BCR functions in BLNK-deficient DT40 B cells. This could be attributable to inability of SLP-76 to be recruited into glycolipid-enriched microdomains (GEMS) after antigen receptor cross-linking. Supporting this idea, the BCR function can be restored when a membrane-associated SLP-76 chimera is enforcedly localized to GEMS. Moreover, addition of both LAT and Gads to SLP-76 allows SLP-76 to be recruited into GEMs, whereby the BCR function is reconstituted. The Gads function can be replaced by overexpression of Grb2.In contrast to SLP-76.BLNK did not require Grb2 families for its recruitment to GEMs. Hence, these data suggest a functional overlap between BLNK and SLP-76, while emphasizing the difference in requirement for additional adaptor molecules in their targeting to GEMs.
Drs. Clark and Kurosaki coworked the function of Bam32, another adaptor molecule, in BCR signaling. By analyzing Bam32-deficient DT40 B cells, we have provided the evidence that Bam32 is involved in BCR-mediated/calcium pathway, presumably explaining the defective NF-AT and NF-KB activation.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Craxton, A.et al.: "Syk and Bruton's tyrosine kinase are required for B cell antigen receptor-mediated activation of the kinase Akt"J. Biol. Chem. 274. 30644-30650 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurosaki, T.et al.: "Genetic analysis of B cell antigen receptor signaling"Annu. Rev. Immunol. 17. 555-592 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishiai, M.et al.: "Involvement of LAT, Gads, and Grb2 in compartmentation of SLP-76 to the plasma membrane"J. Exp. Med.. 192. 847-856 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wong, J.et al.: "Functional complementation of BLNK by SLP-76 and LAT linker proteins. (2000) 275,33116-33122"J. Biol. Chem. 275. 33116-33122 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurosaki, T.et al.: "BLNK : Connecting Syk and Btk to calcium signals"Immunity. 12. 1-5 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurosaki, T.: "Functional dissection of BCR signaling pathways"Curr. Opin. Immunol. 12. 276-281 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurosaki, T.et al.: "Regulation of phospholipase C-γ2 pathway in B cells"Immunol. Rev.. 176. 19-29 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niiro, H.et al.: "The B lymphocyte adaptor molecule of 32 kilodaltons (Bam32) regulates B cell antigen receptor signaling and cell survival"J. Exp. Med. 195. 143-149 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurosaki, T.et al.: "Regulation of phospholipase C-γ2 and phosphoinositide 3-kinase pathways by adaptor proteins in B lymphocytes"Int. Rev. Immunol. 20. 23-37 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Craxton, A. et al.: "Syk and Bruton's tyrosine kinase are required for B cell antigen reeptor-mediated activation of the kinase Akt"J. Biol. Chem.. 274. 30644-30650 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurosaki, T.: "Genetic analysis of B cell antigen receptor signaling"Annu. Rev. Immunol.. 17. 555-592 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishiai, M. et al.: "Involvement of LAT, Gads, and Grb2 in compartmentation of SLP-76 to the plasma membrane."J. Exp. Med.. 192. 847-856 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wong, J. et al.: "Functional complementation of BLNK by SLP-76 and LAT linker proteins"J. Biol. Chem.. 275. 3316-33122 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurosaki, T. et al.: "BLINK : Connecting Syk and Btk to calcium signals"Immunity. 12. 1-5 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurosaki, T.: "Functional dissection of BCR signaling pathways. (2000) Curr. Optin. Immunol. 12, 276-281"Curr. Opi. Immunol.. 12. 276-281 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurosaki, T. et al.: "Regulation of phospholipase C-γ2 pathway in B cells"Immunol. Rev.. 176. 19-29 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niiro, H. et al.: "The B lymphocyte adaptor molecule of 32 kilodaltons (Bam32) regulates B cell antigen receptor signaling and cell survival"J. Exp. Med. 195. 143-149 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inabe, K. et al.: "Vav3 modulates B cell receptor responses by regulating phosphoinositide 3 -kinase activation."J. Exp. Med.. 195. 189-200 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kurosaki, T.: "Regulation of B cell responses by adaptor proteins"Nature Rev. Immunol.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kurosaki, T.: "Regulation of B cell fates by BCR signaling components"Cuff. Opin. Immunol.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishiai,M. et al.: "Involvement of LAT, Gads, and Grb2 in compartmentation of SLP-76 to the plasma membrane."J.Exp.Med.. 192. 847-856 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wong,J. et al.: "Functional complementation of BLNK by SLP-76 and LAT linker proteins."J.Biol.Chem.. 275. 33116-33122 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurosaki,T.and Tsukada,S.: "BLNK : Connecting Syk and Btk to calcium signals."Immunity. 12. 1-5 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurosaki,T.: "Functional dissection of BCR signaling pathways."Curr.Opin.Immunol.. 12. 276-281 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurosaki,T. et al.: "Regulation of phospholipase C-γ2 pathway in B cells."Immunol.Rev.. 176. 19-29 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishiai,M.et al.: "BLNK required for coupling Syk to PLCγ2 and Racl-JNK in B cells."Immunity. 10. 117-125 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishiai,M.et al.: "Association of Phospholipase C-γ2 Src homology 2 domains with BLNK is critical for B cell antigen receptor signaling."J.Immunol.. 163. 1746-1749 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurosaki,T.et al.: "Genetic analysis of B cell antigen receptor signaling."Annu.Rev.Immunol.. 17. 555-592 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurosaki,T.et al.: "BLNK:Connecting Syk and Btk to calcium signals."Immunity.. 12. 1-5 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurosaki,T.: "Functional dissection of BCR signaling molecules."Curr.Opin.Immunol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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

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