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Role of tyrosine phosphatases in lymphocyte signaling

Research Project

Project/Area Number 09044354
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Immunology
Research InstitutionTokyo Metropolitan Institute for Neuroscience

Principal Investigator

YAKURA Hidetaka  Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immunology, Director of Molecular research Division, 微生物学・免疫学研究部門, 参事 (60166486)

Co-Investigator(Kenkyū-buntansha) SCHRAVEN Burkhart  Ruprecht-Karls University of Heidelberg Department of Immunology, Professor, 免疫学, 教授
KORETZKY Gary  University of Iowa College of Medicine, Department of Internal Medicine, Profess, 医学部・内科学, 教授
MIZUNO Kazuya  Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学研究部門, 副参事 (00219643)
KATAGIRI Tatsuo  Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学研究部門, 主事 (00233742)
OGIMOTO Mami  Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学研究部門, 主事 (80158609)
Project Period (FY) 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1997: ¥5,400,000 (Direct Cost: ¥5,400,000)
Keywordstyrpsine phosphatase / signal transduction / lymphocyte / CD45 / PEP / MAP kinase
Research Abstract

This project was initiated to elucidate the function Of protein tyrosine phosphatases (PTPs) in B lymphocyte signaling. We focused on two PTPs : one is a receptor-type PTP,CD45, and the other is an intracellular PTP,PEP.In collaboration with Dr Denis Alexander, we demonstrated (1) that CD45 regulates BCR-induced Erk activation and JNK/p38 activation separately, (2) that regulation exerted by CD45 on Erk and JNK/p38 is opposite in immature and mature B cells, and (3) that JNK/p38 activities are correlated with enhanced BCR-induced growth arrest. These results suggest that CD45 regulates members of MAP kinase family differentially and the mode of regulation is distinct depending on the state of differentiation. We previously reported that tyrosine Phosphorylation of a protein Of 66 kDa is defective in CD45-deficient clones, implying that this protein may be a downstream target of CD45. Together with Dr Burkhart Schraven's group, we are in the process of characterizing the nature of a protein of 66 kDa using 2-D gel electrophoresis. Collaborative efforts with Dr Gary Koretzky's group showed that introduction of antisense PEP cDNA into WEHI-231 cells rescued almost completely BCR-induced growth arrest and apoptosis, suggesting that PEP is a positive and essential molecule for BCR signal transduction.
All these results, together with collaborators' work, were presented at the TMIN International Symposium organized by the head investigator and were published as the proceedings entitled "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" from Springer-Verlag.

Report

(2 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Yakura,H: "Protein tyrosine phosphatases in B lymphocyte signal transduction" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling (ed,Yakura,H)Springer-Verlag,Tokyo. 134-146 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hasegawa,K: "Role of PEST domain tyrosine phosphatase PEP in B cell antigen receptorinduced signaling" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling (ed,Yakura,H)Springer-Verlag,Tokyo. 325-326 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Katagiri,T: "CD45 differentially regulates B cell antigen receptor-mediated tyrosine phosphorylation in immature and mature B cells" Kinases and Phosphatasesin Lymphocyte and Neuronal Signaling (ed,Yakura,H)Springer-Verlag,Tokyo. 328-329 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ogimoto,M: "Regulation of MAP kinases and NF-kB activation by CD45 in WEHI-231 and BAL-17 B cells" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling (ed,Yakura,H)Springer-Verlag,Tokyo. 330-331 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Arimura,Y: "Role of CD45 in CD40 signaling in mature B lymphoma cells" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling (ed,Yakura,H)Springer-Verlag,Tokyo. 334-335 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mizuno,K: "SHP-1 is involved in neuronal differentiation of P19 embryonic carcinoma cells" FEBS Lett. 417. 6-12 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yakura,H: "Protein tyrosine phosphatases in lymphocyte signaling" Immunology Today. In press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yakura,H(ed): "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" Springer-Verlag,Tokyo, 368 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mizuno, K,Katagiri, T,Maruyama, E,Hasegawa, K,Ogimoto, M,and yakura, H: "SHP-1 is involved in neuronal differentiation of P19 embryonic carcinoma cells." FEBS Lett. 417. 6-12 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yakura, H: "Protein tyrosine phosphatases in lymphocyte signaling" Immnology Today. (In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yakura, H,Katagiri, T,Ogimoto, M,Hasegawa, K,Arimura, Y,Mitomo, K,and Mizuno, K: rotein tyrosine phosphatases in B lymphocyte signal transduction. "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling". (ed, Yakura, H) Springer-Verlag, Tokyo, 134-146 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hasegawa, K,Katagiri, T,Ogimoto, M,Arimura, Y,Mizuno, K,Mitomo, K,and Yakura, H: Role of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced signaling. "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling.". (ed, Yakura, H) Springer-Verlag, Tokyo, 325-326 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Katagiri, T,Ogimoto, M,Hasegawa, K,Arimura, Y,Mitomo, K,Mizuno, K,Yakura, H: CD45 differentially regulates B cell antigen receptor-mediated tyrosine phosphorylation in immature and mature B cells. "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling. (ed, Yakura, H) Springer-Verlag, Tokyo", 328-329 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ogimoto, M,Arimura, Y,Mitomo, K,Katagiri, T,Hasegawa, K,Mizuno, K,and Yakura, H: Regulation of MAP kinases and NF-kB activation by CD45 in WEHI-231 and BAL-17 B cells. "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling". (ed, Yakura, H) Springer-Verlag, Tokyo, 330-331 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Arimura, Y,Ogimoto, M,Mitomo, K,Katagiri, T,Hasegawa, K,mizuno, K,and Yakura, H: Role of CD45 in CD40 signaling in mature B lymphoma cells. "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling". (ed, Yakura, H) Springer-Verlag, Tokyo, 334-335 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yakura, H: "Protein tyrosine phosphatases in B lymphocyte signal transduction" Kinases and Phosphatases in Lymphocyte and Neuronal Signalig(ed,Yakura,H)Springer-Verlag,Tokyo. 134-146 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hasegawa, K: "Role of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced signalig" Kinases and phosphatases in Lymphocyte and Neuronal Signaling(ed,Yakura,H)Springer-Verlag,Tokyo. 325-326 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Katagiri, T: "CD45 differentially regulates B cell antigen receptou-mediated tyrosine phosphorylation in immature and mature B cells" Kinases and phosphatasesin Lymphocyte and Neuronal Signaling(ed,Yakura,H)Springer-Verlag,Tokyo. 328-329 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ogimoto, M: "Regulation of MAP kinases and NF-kB activation by CD45 in WEHI-231 and BAL-17 B cells" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling(ed,Yakura,H)Springer-Verlag,Tokyo. 330-331 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Arimura, Y: "Role of CD45 in CD40 signaling in mature B lymphoma cells" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling(ed,Yakura,H)Springer-Verlag,Tokyo. 334-335 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mizuno, K: "SHP-1 is involved in neuronal differentiation of P19 embryonic carcinoma cells" FEBS Lett. 417. 6-12 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yakura, H: "Protein tyrosine phoshatases in lymphocyte signaling" Immunology Today. (In press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yakura, H(ed): "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" Springer-Verlag,Tokyo, 368 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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