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

Regulation of B cell antigen receptor-mediated signaling by SHP-1

Research Project

Project/Area Number 09836008
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 免疫の制御機構
Research InstitutionTokyo Metropolitan Institute for Neuroscience

Principal Investigator

MIZUNO Kazuya  Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology and Immunology Research Scientist, 微生物学・免疫学研究部門, 副参事研究員 (00219643)

Co-Investigator(Kenkyū-buntansha) YAKURA Hidetaka  Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology and Im, 微生物学・免疫学研究部門, 参事研究員 (60166486)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsprotein tyrosine phosphatase / tyrosine phosphorylatio / SHP-1 / SH2 domain / MAPkinase / apoptotic cell death / B細胞抗原受容体 / シグナル伝達 / SLP-76
Research Abstract

By using mouse immature B cell line, WEHI-231, we have investigated how SHP-1 and SHP-1-associated molecules, cytoplasmic proteintyrosine phosphatase (PTP) containing two SH2 domains, regulate B cell antigen receptor (BCR)-mediated signaling event, especially MAP kinase (MAPK) pathways which play important roles in cell proliferation, differentiation and apoptotic cell death. The results obtained are follows ;
(1) WEHI-231 cells were transfected with cDNA encoding wild-type SHP-1 (SHP-1-wt) or mutant SHP-1 (SHP-1-CS) which lacks PTP activity by substituting Cys to Ser in PTP domain. Then, the activity of each member of MAPK family was measured by Western blotting using antibodies against phosphorylated forms of MAPKs. ERK activity in SHP-1-wt or SHP-1-CS transfectant after the stimulation with anti-IgM Ab was almost identical to that in untransfected control cells, whereas anti-IgM-induced JNK and p38 activities in both transfectants were enhanced when compared to those in control cells … More . It should be noted that enhancement of JNK activity after anti-IgM stimulation was most prominent. In addition, SHP-1-wt transfectant showed enhanced anti-IgM-induced apoptotic cell death.
(2) We have previously showen that SHP-1 is constitutively associated with SLP-76, leukocyte specific protein containing a SH2 domain at its C terminus. Next, WEHI-231 cells were transfected with cDNA encoding wild-type or mutant forms of SLP-76 and anti-IgM-induced MAPK activation was analyzed in these transfectants. There are little differences in the degree of activities of three MAPK members between untransfected and transfected cells. In contrast, anti-IgM-induced cell death was significantly suppressed in the cells transfected with mutant SLP-76 whose SH2 domain fails to bind phosphorylated Tyr residues.
(3) When cells were transfected with SHP-1-CS-encoding cDNA, tyrosine phosphorylation of several proteins were enhanced after anti-IgM stimulation. We focused on one protein whose phosphorylation was most enhanced as a candidate for the SHP-1 substrate and characterized its nature. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Hasegawa,K.et al.: "Requirement of PEST Domain Tyrosine Phosphatase PEP in B Cell Receptor-initiated Growth Arrest and Apoptosis." Eur.J.Immunol.(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yakura,H.: "Phosphatases and kinases in lymphocyle signaling" Immunol.Today. 19. 198-201 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizuno,K.,et al: "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
      1998 Final Research Report Summary
  • [Publications] Yakura,H.,et al: "Protein tyrosine phosphatases in B lymphocyte signaling" Kinases and Phosphatases in Lymphocyte and Neuroral Signaling. 134-146 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizuno,K.,et al: "Possible involvement of Src homology region 2 domain-containing phosphatase-1,SHP-1,in neuronal differentiation" Kinases and Phosphatases in lymphocyte and Neuronal Signaling. 310-311 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uetani,N.,et al: "Targeted disruption of the murine protein tyrosine phosphatase delta (MPTP8) gene results in growth retardation and behavioral abnormaloties" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling. 313-314 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hasegawa,K.,at al: "Role of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced signaling" Kinases and Phosphatases in Lymphocyte and Neuronal signaling. 325-326 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Katagiri,T.,et al: "CD45 differeutially regulates B cell antigen receptor-mediated tynosine phospharyhton in immature and mature B cells" Kinases and Phosphatases in Lymhocyte and Neuronal Signaling. 328-329 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ogimoto,M.,et al: "Regulation of MAPKinases and NF-KB activation by CD45 in WEHI-231 and BAL-17 B cells" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling. 330-331 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Arimura,Y.,et al: "Role of CD45 in CD40 signaling in mature B lymphoma cells" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling. 334-335 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hasegawa, K., et al.: "Requirement of PEST Domain Tyrosine Phosphatase PEP in B Cell Receptor-initiated Growth Arrest and Apoptosis." Eur.J.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yakura H: "Phosphatases and kinases in lymphocyte signaling." Immunol Today. 19. 198-201 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Adachi T, Flaswinkel H, Yakura H, Reth M,& Tsubata T: "The B cell surface protein CD72 recruits the tyrosine phosphatase SHP-1 upon tyrosine phosphorylation." J Immunol. 160. 4662-4665 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 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
      1998 Final Research Report Summary
  • [Publications] Yakura H, Katagiri T, Ogimoto M, Hasegawa K, Arimura Y, Mitomo, K,& Mizuno, K.: "Protein tyrosine phosphatases in B lymphocyte signaling." In "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
      1998 Final Research Report Summary
  • [Publications] Mizuno K, Katagiri T, Hasegawa K, Arimura Y, Mitomo K, Ogimoto M,& Yakura H: "Possible involvement of Src homology region 2 domain-containing phosphatase-1, SHP-1, in neuronal differentiation." In"Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" (ed, Yakura H) Springer-Verlag, Tokyo.310-311 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uetani N, Asano M, Mizuno K, Yakura H,& Iwakura Y: "Targeted disruption of the murine protein tyrosine phosphatase delta (MPTPdelta) gene results in growth retardation and behavioral abnormalities." In"Kinases and Phosphatases in Lymphocyte and Neuronal Signaling" (ed, Yakura H) Springer-Verlag, Tokyo.313-314 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hasegawa K, Katagiri T, Ogimoto M, Arimura Y, Mizuno K, Mitomo K,& Yakura H: "Role of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced signaling." In"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
      1998 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." In"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
      1998 Final Research Report Summary
  • [Publications] Ogimoto M, Arimura Y, Mitomo K, Katagiri T, Hasegawa K, Mizuno K,& Yakura H: "Regulation of MAP kinases and NF-kappaB activation by CD45 in WEHI-231 and BAL-17 B cells" In"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
      1998 Final Research Report Summary
  • [Publications] Arimura Y, Ogimoto M, Mitomo K, Katagiri T, Hasegawa K, Mizuno K,& Yakura H: "Role of CD45 in CD40 signaling in mature B lymphoma cells." In"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
      1998 Final Research Report Summary
  • [Publications] Hasegawa,K.et al: "Requirement of PEST Domain Tyrosine Phosphatase PEP in B Cell Receptor-initiated Growth Arrest and Apoptosis" Eur.J.Immunol.(印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizuno,K: "Possible involvement of Src homology region 2 domain-containing phosphatase-1,SHP-1,in neuronal differentiation" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling(ed,Yakura,H)Springer-Verlag,Tokyo. 310-311 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Uetani,N: "Targeted disruption of the murine protein tyrosine phosphatase δ(MPTPδ)gene results in growth retardation and behavioral abnormalities" Kinases and Phosphatases in Lymphocyte and Neuronal Signaling(ed,Yakura,H)Springer-Verlag,Tokyo. 313-314 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hasegawa,K: "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)

    • Related Report
      1997 Annual Research Report
  • [Publications] Katagiri,T: "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)

    • 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

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi