The role of Biuton's tyrosine kinase, Btk, on murine B cell activation

• Project/Area Number: 09836002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 免疫の制御機構
• Research Institution: The Kitasato Institute
• Principal Investigator: KIKUCHI Yuji Center for Basic Research, Kitasato Institute, Chief, 基礎研究所, 室長 (60262078)
• Project Period (FY): 1997 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥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)
• Keywords: Immunodeficiency / signal transduction / Btk / tyrosine kinase / CD38 / XID / PH領域

Research Abstract

Bruton's tyrosine kinase (Btk) is a member of a Btk/Tec family of cytoplasmic tyrosine kinases, and is required for normal B cell development and signal transduction through cell surface functional molecules.In this project, we investigated the regulatory mechanism of Btk activity and its signaling pathway by using Fyn- and/or Lyn-deficient B cells.We also identified the molecule that associates with the PH domain of Btk.
[Results]
1. Either Fyn- or Lyn-deficient B cells have reduced proliferative responses to CS/2 (CD38 ligation), and Fyn-/Lyn-double deficient B cells hardly respond to CS/2, even if in the presence of IL-5.
2. In Lyn- or Fyn-/Lyn-double deficient B cells, Btk is not phosphorylated by CD38 ligation. B cells from Fyn-deficient mice showed significant tyrosine phosphorylation of Btk
3. We isolated full length cDNA clone which encodes the molecules that interact with the PH domain of Btk.It encodes 547 amino acid residues and contains serine rich domains. It has 89% identity with human LTGI9 in amino acid level.
4. The region responsible for the association with Btk was seemed to be located between amino acid residues 214 and 256 from the amino terminus of BAM#11.

Research Products

• [Publications] Yasue,T.et al.: "A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5." Proc.Natl.Acad.Sci.USA.94. 10307-10312 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ogata,N.et al.: "The activation of the JAK2/STAT5 pathway is commonly involved in signaling through the human IL-5 receptor." Int.Arch.Allergy.Immunol.114. 24-27 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Baba,M.et al.: "Mouse germinal center B cells with the xid mutation retain responsiveness to anti-mouse CD40 antibodies but diminish IL-5 responsiveness." Intl.Immunol.9. 1463-1473 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yasue, T.et al.: "A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5." Proc. Natl. Acad. Sci. USA.94. 10307-10312 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] OGATA, N.et al.: "The activation of the JAK2/STAT5 pathway is commonly involved in signaling through the human IL-5 receptor." Int. Arch. Allergy. Immunol.114. 24-27 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Baba. M.et al.: "Mouse germinal center B cells with the xid mutation retain responsiveness to anti-mouse CD40 antibodies but diminish IL-5 responsiveness." Intl. Immunol.9. 1463-1473 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yasue,T.et al.: "A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5." Proc. Natl.Acad.Sci.USA.94. 10307-10312 (1997)
• [Publications] Baba,M.et al.: "Mouse germinal center B cells with the xid mutation retain responsiveness to anti-mouse CD40 antibodies but dimmish IL-5 responsiveness." Intl.Immunol.9. 1463-1473 (1997)
• [Publications] Ogata,N.et al.: "The activation of the JAK2/STAT5 pathway is commonly involved in signaling through the human IL-5 receptor." Int.Arch.Allergy.Immunol.114. 24-27 (1997)