Grant-in-Aid for Scientific Research on Priority Areas (A)
|Research Institution||Gifu University|
日高 弘義 名大, 医学部, 教授 (80100171)
SUZUKI Masaaki Gifu Univ., Faculty of Engineering, Professor, 工学部, 教授 (90093046)
野島 庄七 東京大学, 名誉教授 (70090470)
永井 克孝 三菱化学生命科学研究所, 所長 (80072974)
IINO Masamitsu Univ. of Tokyo, Graduate School pf Med. Pharmacol., Professor, 大学院・医学系研究科, 教授 (50133939)
ICHIKAWA Atsushi Kyoto Univ., Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (10025695)
YAMAMURA Hirohei Kobe Univ., Faculty of Medicine, Professor, 医学部, 教授 (90030882)
|Project Fiscal Year
1999 – 1999
Adopted(Fiscal Year 1999)
|Budget Amount *help
¥59,400,000 (Direct Cost : ¥59,400,000)
Fiscal Year 1999 : ¥2,900,000 (Direct Cost : ¥2,900,000)
Fiscal Year 1998 : ¥26,500,000 (Direct Cost : ¥26,500,000)
Fiscal Year 1997 : ¥30,000,000 (Direct Cost : ¥30,000,000)
|Keywords||受容体機能解析 / カルシウムシグナル / プロテインキナーゼ / 分子設計 / 有機合成 / 機能探索分子 / Receptor / Prostaglandin / Calciun / Kinese / Molecular Probe / Imagining / 受容体 / プロスタグランジン / カルシウム / キナーゼ / 探索分子 / イメージング / 受容体の機能解析 / 情報分子の可視化 / 合成化合物 / セカンドメッセンジャー / 構造機能解析|
This research program obtained the following fruitful results.
1. Distinct domains, relating to the association and activation steps of G-protein in EP3 subtype PG receptor and to the recognition of the ring structure and a side chain of PG in IP/DP receptors, were separately identified. Many of PG receptor deficient mice were developed and utilized for the analysis of phenotypic appearance.
2. Development of assay system to search for the natural ligands bound to opioid/nociceptin and muscarin receptor subtypes was established.
3. Pyk2, a downstream mediator of IL-2 receptor-coupled Jak signaling pathway, was discovered.
4. Biological functions of Midkine and Basigin were elucidated.
5. CaィイD12+ィエD1 oscillations in endothelial cells were proven to induce release of NO, which decreased the CaィイD12+ィエD1 frequency in vascular smooth muscle cells. The assay system for the analysis of IPィイD23ィエD2R subtype was established.
6. In pancreatic β cells, exocytosis of insulin-containing vesicles was fo
und to depend not only on CaィイD12+ィエD1 but also on the A-kinase activities.
7. A novel kinase that bound SF2 and regulated transcription was discovered.
8. The distinctive roles of Syk in oxidative and osmotic stress signaling were elucidated.
9. A novel kinase hCds1 that functioned in G2/M check point mechanism in response to DNA damage was cloned.
10. The possible involvement of caspase 3 activation by C2-ceramid in the apoptosis of PC 12 cells induced by low-oxygen stress was proposed.
11. GIF-0082, a novel ligand that specifically effected on PCR but not on CICR, which is different from that of dantoloren, was developed based on the structure-activity studies.
12. 15R-TIC having high binding affinity and selectivity for a novel prostacyclin receptor subtype (IPィイD22ィエD2) in the central nervous system was created. The specific location of the IPィイD22ィエD2 was visualized by positron emission tomography (PET) of a living rhesus monkey using ィイD111ィエD1C-labeled 15R -TIC.
13. A novel hybrid molecule of phorbol ester and phosphatidylserine that inhibited PKC was synthesized. A newly designed photoaffinity probe succeeded in the labeling of a PKC isozyme.
14. The CaィイD12+ィエD1 binding domain of calcium channel in the heart muscle was clarified by using a novel CaィイD12+ィエD1 antagonist. Development of hypersensitive detection system for photoaffinity labeling was also established. Less