| Project/Area Number |
14207044
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | The UNIVERSITY OF TOKYO |
|---|
Principal Investigator |
IIRI Taroh The UNIVERSITY OF TOKYO, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (90313022)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUJITA Toshiro The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (10114125)
OHNISHI Hirohide JICHI MEDICAL SCHOOL, DEPARTMENT OF MEDICINE, LECTURER, 非常勤講師 (00313023)
MAKITA Noriko The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (60353455)
MOTOKURA Toru The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (00192823)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥38,610,000 (Direct Cost: ¥29,700,000、Indirect Cost: ¥8,910,000)
Fiscal Year 2004: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2003: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2002: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
|
|---|
| Keywords | G PROTEIN / RECEPTOR / MOLECULAR MECHANISM / G PROTEIN DISEASE / GENE THERAPY / DESENSITIZATION / CARDIOMEGALY / INVERSE AGONIST |
|---|
| Research Abstract |
1)ELUCIDATION OF ACTION MECHANISM OF G PROTEINS BASED ON ANALYSES OF G PROTEIN DISEASES : We have produced a model of receptor-dependent activation of G protein. In this study, we analyzed a newly discovered AVDT mutant of Gas, which turned out to act in a dominant negative fashion.
2)NEW ACTIVATION MECHANISM OF G PROTEIN-COUPLED RECEPTOR AND DISEASES : (1)We have shown that mechanical stress activates AT1 independent of angiotensin II. (2)Some AT1 receptor blockers were shown to inhibit this autonomous activation of AT1 by acting as inverse agonists to AT1. (3)We have also shown activation and regulation of desensitization of GPCRs
3)DEVELOPMENT OF METHODS TO DIFFERENTIATE AND CONTROL G PROTON-DEPENDENT SIGNALS : Based on a model of receptor-dependent activation G protein, we have designed G protein α/βγ mutants that inhibit activation of GPCRs and G proteins.
4)DEVELOPMENT OF SELECTIVE GENE TRANSFER METHODS : By using DEAE-Adenovirus method, we developed an easy method to enable gene transfer to the cells or model animals
|
