| Project/Area Number |
12490024
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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 |
広領域
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| Research Institution | NARA INSTITUTE OF SCIENCE AND TECHNOLOGY |
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Principal Investigator |
HAKOSHIMA Toshio NARA INSTITUTE OF SCIENCE AND TECHNOLOGY, DEPARTMENT OF BIOLOGICAL SCIENCE, PROFESSOR, バイオサイエンス研究科, 教授 (00164773)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Kengo NARA INSTITUTE OF SCIENCE AND TECHNOLOGY, DEPARTMENT OF BIOLOGICAL SCIENCE, RESEARCH ASSOCIATE, バイオサイエンス研究科, 助手 (60304169)
清水 敏之 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助手 (30273858)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2001: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2000: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | Rho / ICAM-2 / PTP2 / cytoskeleton / adhesion molecules |
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| Research Abstract |
ERM (ezrin/radixin/moesin) proteins play a key role in the formation of the membrane-associated cytoskeleton by linking actin filaments and adhesion molecules such as CD44, CD43 and ICAMs, immunoglobulin-family adhesion molecules. ERM proteins also bind sodium and hydrogen ion exchanger regulatory factors (NHERFs), which interact with the ion channel NHE to modify the channel activity. These binding activities of ERM proteins are initiated by binding to phosphatidylinositol 4,5-bisphosphate (PP2) in the downstream of the Rho signaling pathway. Interestingly, the N-terminal conserved domain of ERM proteins, the PERM (4. 1 and ERM) domain, mediates the multiple interactions with IPS, ICAM-2, and RhoGDL We have determined the crystal structures of the radixin PERM domain complexefl with these binding partners and discussed the molecular mechanisms by which ERM proteins accomplish the multiple molecular recognition. Based on the three-dimensional structures of the complexes, we have addressed possible ERM-binding partners including LI-CAM. We have also determined the PERM domain of merlin, which is a gene product of NF n and elucidated the structural and functional effects of several mutations obtained from NF n patients. Finally, we have succeeded to determine the crystal structure of the Rho-binding domain of Rho-kinase and clarified the similarity and dissimilarity of the domain compared with that of protein kinase N.
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