Ubiquitin system of Src-Cbl negatively regulating the signal transduction of osteoclasts in rheumatoid arthritis
| Project/Area Number |
13671522
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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 |
Orthopaedic surgery
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| Research Institution | Kagoshima University |
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Principal Investigator |
KOMIYA Setsuro Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (30178371)
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| Co-Investigator(Kenkyū-buntansha) |
IJIRI Kosei Kagoshima University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (00315417)
MATSUNAGA Shunji Kagoshima University, University Hospital, Faculty of Medicine, Assistant Professor, 医学部附属病院, 講師 (90229500)
YONE Kazunori Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (40182844)
YOKOUCHI Masahiro Kagoshima University, Faculty of Medicine, Research Associate, 医学部, 助手
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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 |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Rheumatoid arthritis / Signal transduction / Src / Cbl / 骨吸収 / 破骨細胞 / ユビキチン / c-Cbl |
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| Research Abstract |
Rheumatoid arthritis (RA) is a local and systemic disease induced by an immune imbalance in joints. A certain antigen in the composite of joint induces the proliferation of lymphocytes, macrophages, plasma cells, and fibroblasts in the synovia, which are responsive for the production of many cytokines including tumor necrosis factor α, interleukin-6, and -1. These cytokines stimulate fibroblasts or osteoblasts to produce RANKL which is necessary for the differentiation of immature cells in the line of macrophage into osteoclasts. Src, non-receptor tyrosine kinase, is responsible for the formation of ruffled border in osteoclasts. The aim of this study was to clarify the mechanism to regulate the formation of osteoclasts responsible for the joint destruction in RA, from the view point of signal transduction, focusing on the Src and the protooncogene c-Cbl. We demonstrated that c-Cbl mediated the ubiquitination of c-Src, by forming the stable complex with the ubiquitin-conjugating enzyme UbcH7, and acting as an E3 ubiquitin ligase for activated receptor tyrosine kinases, thereby down-regulating Src.
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Report
(3 results)
Research Products
(11 results)
