| Project/Area Number |
14570408
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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 |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HONDA Zem-ichiro The University of Tokyo, FAOM, Professor, 医学部附属病院, 講師 (70238814)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Masato Osaka University, Research Inst. For Microbial, Dis. Professor, 微生物研究所, 教授 (10177058)
TSUCHIYA Noyuki The University of Tokyo, Gr.Stud.. for Med. and FAOM, Associate Professor, 大学院・医学系研究科, 助教授 (60231437)
SUZUKI Takeshi The University of Tokyo, FAOM, Assistant Professor, 医学部附属病院, 助手 (50272555)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | lipid rafts / FcγRIIB / systemic lupus erythematosus / Src family kinas / 脂質ラフト / 微小管 / Src family kinase / Fe受容体 / srcフォミリーキナーゼ / SH3ドメイン / FeγRIIb |
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| Research Abstract |
FcγRIIB, a tow-affinity lgG receptor, possesses inhibitory potential on B cell antigen receptor (BCR) signaling and contributes to balance immune responses in vivo. We have recently described a novel polymorphism, FcγRIIB lle232Thr, and its association with susceptibility to systemic lupus erythematosus (SLE) in Asians. Here we show that lle232Thr substitution impairs the ability of FcγRIIB to inhibit 8CR signaling related to phosphatidylinostol-(3 14,5)-trisphosphate synthesis. Intriguingly, Fcγ RIIB-232Thr showed reduced association with specialized membrane microdomains, referred to as lipid rafts, thus providing mechanistic basis for the reduced inhibitory potential of the allele. This is the first demonstration of disease-associated receptor polymorphism resulting in altered membrane compartmentalization, and may provide novel mechanisms that potentially contribute to aberrant B cell regulation in SLE patients possessing FCGR2B-232Thr/Thr genotype.
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