Molecular cloning and function of CD44 cytoplasmic domain associated molecules
| Project/Area Number |
15390122
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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 |
Experimental pathology
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| Research Institution | Chiba University |
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Principal Investigator |
HARIGAYA Kenichi Chiba Univ., Grad.Sch.of Med., Professor, 大学院・医学研究院, 教授 (40101894)
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| Co-Investigator(Kenkyū-buntansha) |
KITAGAWA Motoo Chiba Univ., Grad.Sch.of Med., Associate Professor, 大学院・医学研究院, 助教授 (40262026)
HIGASHI Morihiro Chiba Univ., Grad.Sch.of Med., Assistant Professor, 大学院・医学研究院, 助手 (00323395)
KAWANA Hidetada Chiba Univ., Grad.Sch.of Med., Assistant Professor, 大学院・医学研究院, 助手 (80359596)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | yeast-two hybrid / cell motility / hMena / RanBPM / CD44 / CD44 knockout mice / NFkB / Toll-like receptor / 遺伝子 / 癌 / 生体分子 / 蛋白質 / CD44シグナリング / RhoA |
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| Research Abstract |
To elucidate the role of CD44 in the inflammation and cancer, the molecules associated with cytoplasmic domain of CD44 were surveyed in HeLa cell cDNA library by yeast-two hybrid system. DNA fragments of RanBPM and hMena were isolated and, then, their cDNAs were cloned from HeLa cell cDNA library. Transfection of short interference RNA from RanBPM into HeLa S3 cells suppressed the cell motility on CD44 stimulation, whereas transfection of si-RNA from hMena induced the cell motility without any stimulation. Both siRNAs affected on the activation of Rho GTPases and the formation of cortical F-actin. These results indicate that CD44 molecule mediates the Rho GTPases activation and, then, modulates cortical F-actin assembly. Thus, our study showed that CD44 would regulate cell shape and motility through Rho GTPase signaling. We also examined the role of CD44 in zymosan-induced arthritis of CD44 (+/+) and (-/-) mice. The severe inflammatory response was always found in CD44 (-/-) mice compared to CD44 (+/+) mice. In the process of the arthritis, the signaling from Toll-like receptors to NFκB was enhanced in CD44 (-/-) mice compared to wild mice. Our results indicate that CD44 would regulate the Toll-like receptor signaling.
Summary : Our studies showed that CD44 molecule play a pivotal role on the regulation of inflammation and tumor cell behavior through its interaction with molecules residing at the plasma membrane and/or in the cytoplasm. Further precise study of the mechanism of CD44 action will provide the useful information of molecular target therapy in inflammation and cancer.
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Report
(4 results)
Research Products
(19 results)
