| Project/Area Number |
08457110
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | The Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
KARASUYAMA Hajime The Tokyo Metropolitan Institute of Medical Science, Dept.of Immunology, Researcher, 免疫研究部門, 研究員 (60195013)
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| Co-Investigator(Kenkyū-buntansha) |
北村 ふじ子 (財)東京都臨床医学総合研究所, 免疫研究部門, 研究員 (90124453)
反町 典子 (財)東京都臨床医学総合研究所, 免疫研究部門, 研究員 (30217468)
杭田 慶介 (財)東京都臨床医学総合研究所, 免疫研究部門, 研究員 (70225126)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | surrogate light chain / preB cell receptor / B cell development / signal transduction / proB cell / preB cell / Igbeta / LOK / キナーゼ / リンパ球 |
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| Research Abstract |
The preB cell receptor (preBCR), composed of muheavy chain, VpreB/lambda5 surrogate light chain and Igalpha/Igbeta heterodimer, is expressed transiently at the large preB cell stage of B cell development. Identification of molecules involved in the preBCR signaling is essential for elucidating the mechanism how preBCR governs B cell differentiation. In the present study, we have established a novel system that provides a superior way to analyze the signal transduction of preBCR by using bone marrow proB cells stimulated in vivo and ex vivo.
When RAG-2^<-1-> mice were treated with an anti-Igbeta mAb, developmentally-arrested proB cells were induced to differentiate to the small preB cell stage. This indicates that the cross-linking of Igbeta on proB cells elicits differentiation signals analogouw to those delivered by preBCR in normal B cell development. The biochemical analyzes revealed that the cross-linking of Igbeta induced a rapid and transient tyrosine phosphorylation of Igalpha, Sky, P13-kinase, Vav and SLP-76 as well as the activation of MAP kinase ERK in proB cells. Intriguingly, the tyrosine phosphorylation of a protein (s) of 35-40kD was evident in proB cells stimulated with the anti-Igbeta mAb but not in B cells stimulated in the same way. We are in the process of identifying the nature of this molecule (s).
We have cloned from preB cells a gene coding for a novel serine/threonine kinase, LOK,which is expressed predominantly in lymphocytes. LOK has a kinase domain, which shows some homology to that of a yeast MAPKKKK STE20 in yeast, as well as a proline-rich region and a coiled-coil region. In order to clarify the function of LOK in lymphocytes, we are currently establishing and analyzing mice deficient for LOK.
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