1998 Fiscal Year Final Research Report Summary
The role of Biuton's tyrosine kinase, Btk, on murine B cell activation
| Project/Area Number |
09836002
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
免疫の制御機構
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| Research Institution | The Kitasato Institute |
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Principal Investigator |
KIKUCHI Yuji Center for Basic Research, Kitasato Institute, Chief, 基礎研究所, 室長 (60262078)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Immunodeficiency / signal transduction / Btk / tyrosine kinase / CD38 / XID |
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| 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.
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