SYNERGISTIC REGULATION OF PHOSPHOINOSITIDE 3-KINASE
Project/Area Number |
12470502
|
Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | HIROSHIMA UNIVERSITY |
Principal Investigator |
HAZEKI Osamu HIROSHIMA UNIVERSITY, GRADUATE SCHOOL OF BIOMEDICALSC1ENCES, PROFESSOR, 大学院・医歯薬学総合研究科, 教授 (80142751)
|
Co-Investigator(Kenkyū-buntansha) |
OKAMURA Naoki HIROSHIMA UNIVERSITY, GRADUATE SCHOOL OF BIOMEDICAL SCIENCES, ASSISTANT PROFESSOR, 大学院・医歯薬学総合研究科, 講師 (30144827)
黒川 知則 広島大学, 医学部, 助教授 (00124793)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥4,700,000 (Direct Cost: ¥4,700,000)
|
Keywords | PHOSPHOINOSITIDE 3-KINASE / INSULIN / BETAGAMMA SUBUNITS / SYNERGISM / ADENOSINE / TYROSINE KINASE / p110β / イノシトールリン脂質3キナーゼ / GTP結合タンパク質 / トランスアクティベーション / 三量体型G蛋白質 |
Research Abstract |
The following results were obtained by establishing the Chinese hamster ovary cells stably expressing GTP-binding protein-coupled receptors, adenosine A1 receptors or fMLP receptors: (1) Adenosine orfMLP activated Akt in the cells (2) This activation was-synergistically increased by insulin (3) The effect of adenosine was abolished by treatment of the cells with pertussis toxin or transfection with beta ARK-CT peptide (4) expression of the p85 regulatory subunit of PI 3-kinase inhibited the action of adenosine (5) expression of p110beta increased markedly the action of adenosine (6) Kinase-dead p110beta prevented the action of adenosine (7) Kinase-dead p110alpha showed little effect (8) An inhibitor of tyrosine kinases inhibited the action of adenosine but a Src family-specific inhibitor PP2 had no effect (9) PP2 prevented the adenosine-induced Erk activation. These results indicated that GPCR activates Akt by a Gbetagama and p110beta-dependent pathway. Tyrosine kinase other than Src family members is also necessary for this activation.
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Report
(4 results)
Research Products
(13 results)