| Project/Area Number |
13670451
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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 |
SUZUKI Takeshi The University of Tokyo, Allergy and Rheumatology, Research Associate, 医学部附属病院, 助手 (50272555)
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| Co-Investigator(Kenkyū-buntansha) |
TSUCHIYA Naouki The University of Tokyo, Human genetics, Associate Professor, 大学院・医学系研究科, 助教授 (60231437)
OKADE Masato University Osaka, Oncogene Research, Professor, 微生物病研究所, 教授 (10177058)
HONDA Zen-ichiro The University of Tokyo, Allergy and Rheumatology, Lecturer, 医学部附属病院, 講師 (70238814)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Fc receptor / src family kinases / lipid rafts / SH3 domain / FcγRIIb / Fc受容体 / FcrRIIb / C末端Srcキナーゼ |
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| Research Abstract |
Antigen receptors, consists of T and B cell receptors and those for Fc portion of Immunoglobulines (Fc receptors for Igs) play central roles in the initial step of immune regulation. It was assumed that receptor engagement is sensed and converted by Src family kinases (SFKs) to cell-inner events. To elucidate the SFK specificity, we introduced novel strategies and established their requirement and specificity in Fc, and c-Kit and Integrin receptors. Notably, SFKs responsible for Fc receptor signaling are all modified with palmitic acid, and they reside in a membrane domain referred to as 'lipid rafts'. We have also shown that special lipid raft-coalescence is an upstream event to SFK activation. It could be assumed that raft-coalescence provides a field for SFKs transactivate on another. We are searching for the molecule(s) responsible for Fc receptor-mediated lipid raft assembly. Next we have cloned two novel molecules interacting with a SFK, Lyn. One possess RING domain and another is a huge adaptor protein possessing putative Grb2 and PI3K binding sites and GAP domain. Third, we are investigating functional differences in polymorphic forms of negatige regulatory Fc receptor for IgG (FcγRIIb), one of which (rare allele) is genetically linked to systemic lupus erythematodes.
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