Structural and functional analysis of ligand-induced polyubiquitination of platelet-derived growth factor receptor
| Project/Area Number |
07557222
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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 | 試験 |
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| Research Field |
内科学一般
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| Research Institution | Chiba University |
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Principal Investigator |
MORI Seijiro Chiba University School of Medicine Assistant, 医学部, 助手 (50270848)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Yasushi Chiba University School of Medicine Professor, 医学部, 教授 (50101358)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | platelet-derived growth factor receptor / polyubiquitination / ubiquitin / proteasome / 血小板由来増殖因子 / 受容体チロシンキナーゼ |
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| Research Abstract |
We have previously reported that the platelet-derived growth factor (PDGF) receptors are polyubiquitinated as a consequence of ligand binding, and have suggested that the ligand-induced receptor ubiquitination plays a negative regulatory role in mitogenic signaling of the receptor, possible by promoting the efficient degradation of the ligand-activated receptor. In the present study, we have showed that, in addition to the PDGF receptors, the receptors for epidermal growth factor, fibroblast growth factor, and colony-stimulating factor-1, are also ubiquitinated after ligand stimulation, suggesting that the ligand-induced receptor ubiquitination is a general phenomenon observed in most of the monomeric receptor tyrosine kinases. Furthermore, we have proved that the ligand-activated and polyubiquitinated PDGF receptor is quickly degraded by 26S proteasomes inside the cells, thereby intracellular signaling by the receptor is terminated. Our present study establishes the biological significance of a novel mechanism for down-regulation of signal transduction by the receptor, namely, ligand-induced ubiquitination and subsequent proteasomal degradation of the monomeric receptor tyrosine kinases.
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Report
(3 results)
Research Products
(12 results)
