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B cell signaling molecules which regulated by protein tyrosine phosphatase CD45

Research Project

Project/Area Number 11680645
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

KATAGIRI Tatsuo  Tokyo Metropolitan Institute for Neuroscience, Department of Immunology & Signal Transduction, Staff Scientist, 東京都神経科学総合研究所, 研究員 (00233742)

Co-Investigator(Kenkyū-buntansha) YAKURA Hidetaka  Tokyo Metropolitan Institute Neuroscience, Department of Immunology & Signal Transduction, Director of Molecular Research Division, 東京都神経科学総合研究所, 参事研究員 (60166486)
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: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsCD45 / BCR signal / Src-family PTK / Lyn / Fyn / protein tyrosine phosphatase (PTP) / Protein tyrosine kinase (PTK) / raft / ラフト / 成熟B細胞
Research Abstract

CD45 is a critical regulator of T and B cell activation. However, there have been conflicting results as to the mode of CD45 action.
1. To obtain some insights into this problem, we tried to identify substrate PTKs for CD45 in B cells and to determine the dephosphory lation sites of the Src-family PTKs. The results demonstrated that in CD45-deficient clones from the immature B cell line, Lyn was selectively hyperphosphorylated and activated in the absence of B cell receptor (BCR) ligation. CD45 constitutively inactivates Lyn by dephosphorylating both the positive (394) and negative (508) tyrosine residues (J.Immunol. 163 : 1321-1326, 1999).
2. We also examined contribution made by CD45 to BCR-induced activation of mitogen-activated protein kinase (MAPK) family members. We found that CD45 regulated BCR-induced c-Jun NH2-terminal kinase (JNK) and p38. Interestingly, the regulation was depend on B cell differentiation level (FEBS Lett. 490 : 97-101, 2001).
3. CD45 exerts a decisive effect on selective sets of CD40-mediated signaling pathway, dictating B cell fate (J.Biol. Chem. 276 : 8550-8556, 2001).
4. To elucidate the molecular basis of these observations, we are now trying to determine the precise localization of CD45 with Src-family PTK, we utilized glycolipid-enriched membrane fraction (GEM), commonly referred to as lipid raft, as a marker. The preliminary results revealed that CD45 is present in the raft before BCR ligation and is sequestered from the raft after stimulation. These results suggest that CD45 constitutively associated with the raft inactivates, Src-family PTK and BCR ligation somehow sequesters CD45 from the raft, thereby initiating activation cascades.
Thus, we are in the process of revealing the regulatory mechanism of BCR signals by CD45 on lipid raft.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Arimura Yutaka: "CD45 is required for CD40-induced inhibition of DNA synthesis and regulation of c-Jun NH2-terminal kinase and p38 in BAL-17 B Cells."J Biol Chem. 276号. 8550-8556 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogimoto Mami: "Opposing regulation of B cell receptor-induced activation of mitogen-activated protein kinases by CD45."FEBS Lett. 490. 97-101 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuno Kazuya: "SHP-1 dephosphorylates BLNK/SLP-65 and selectively regulates c-Jun NH2-terminal kinase activation in B cells."J Immunol. 165号. 1344-1351 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kumanogoh Atsushi: "SIdentification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100 : A novel mechanism for regulating B cell signaling."Immunity. 13号. 621-631 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Uetani Noriko: "Impaired learning with enhanced hipocampal long-term potentiation in PTP delta-deficient mice."EMBO J. 19号. 2775-2785 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Adachi Takahiro: "CD72 negatively regulates signaling through the antigen recepto og B cells."J Immunol. 164号. 1223-1229 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katagiri Tatsuo: "CD45 negatively regulates Lyn kinase activity by dephosphorylating both positive and negative regulatory tyrosine residues in immature B cells."J Immunol. 163号. 1321-1326 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa Kiminori: "Requirement of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced growth arrest and apoptosis."Eur J Immunol. 29号. 887-896 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arimura Y, Ogimoto M, Mitomo K, Katagiri T, Yamamoto K, Volarevic S, Mizuno K & Yakura H: "CD45 is required for CD40-induced inhibition of DNA synthesis and regulation of c-Jun NH2-terminal kinase and p38 in BAL-17 B cells."J.Biol. Chem.. 276. 8550-8556 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogimoto M, Arimura Y, Katagiri T, Mitomo K, Woodgett JR, Nebreda AR, Mizuno K & Yakura H: "Opposing regulation of B cell receptor-induced activation of mitogen-activated protein kinases by CD45."FEBS Lett. 490. 97-101 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H, hirata H, Iwahor K, Uchida J, Yasui T, Matsumoto M, Yoshida K, Yakura H, Pan C, Parnes JR & Kikkutani Hi: "Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100 : AΛnovel mechanism for regulating B cell singaling."Immunity. 13. 621-631 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuno K, Tagawa Y, Mitomo K, Arimura Y, Hatano N, katagiri T, Ogimoto M & Yakura H: "Src homology region 2 (SH2) domain-containing phosphatase-1 dephosphorylates BLNK/SLP-65 and selectively regulates c-Jun NH2-terminal kinase activation in B cells."J.Immunol.. 165. 1344-1351 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Uetani N, Kato K, Ogura H, Mizuno K, Kawano K, Mikoshiba K, Yakura H, Asano M & † Iwakura Y: "Impaired learning with enhanced hippocampal long-term potentiation in PTP delta-deficient mice."EMBO J.. 19. 2775-2785 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Adachi T, Wakabayashi C, Nakayama T, Yakura H & Tsubata T: "CD72 negatively regulates signaling through the antigen receptor of B cells."J.Immunol. 164. 1223-1229 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katagiri T, Ogimoto M, Hasegawa K, Arimura Y, Mitomo K, Okada M, Clark MR, Mizuno K & Yakura H: "CD45 negatively regulates Lyn activity by dephosphorylating both positive and negative regulatory tyrosine residues in immature B cells."J.Immunol.. 163. 1321-1326 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa K, Yajima H, Katagiri T, Ogimoto M, Arimura Y, Mitomo K, Mashima K, Mizuno K & Yakura H: "Requirement of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced growth arrest and apoptosis."Eur. J.Immunol.. 29. 887-896 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arimura,Y.: "CD45 is required for CD40-induced inhibition of DNA synthesis and regulation of c-Jun NH_2-terminal kinase and p38 in BAL-17 B cells."J.Biol.Chem.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ogimoto,M.: "Opposing regulation of B cell receptor-induced activation of mitogen-activated protein kinases by CD45."FEBS Lett.. 490(1-2). 97-101 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mizuno,K.: "SHP-1 dephosphorylates BLNK/SLP-65 and selectively regulates c-Jun NH_2-ternminal kinase activation in B cells."J.Immunol.. 165. 1344-1351 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hasegawa,K.: "Requirement of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced growth arrest and apoptosis."Eur.J.Immunol.. 29. 887-896 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Katagiri,T.: "CD45 negatively regulates Lyn kinase activity by dephosphorylating both positive and negative regulatory tyrosine residues in immature B cells."J.Immunol.. 163. 1321-1326 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Katagiri Tatsuo, et al.: "CD45 negatively regulates Lyn kinase activity by dephosphorylating both positive and negative regulatory tyrosine residues in immature B cells"Journal of Immunology. 163号. 1321-1326 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hasegawa Kiminori, et al.: "Requirement of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced growth arrest and apoptosis"European Journal of Immunology. 29号. 887-896 (1999)

    • Related Report
      1999 Annual Research Report

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

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