| Project/Area Number |
05271102
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | The University of Tokyo (Faculty of Pharmaceutical Sciences) |
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Principal Investigator |
KATADA Toshiaki Faculty of Pharmaceutical Science, University of Tokyo, Professor, 薬学部, 教授 (10088859)
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| Co-Investigator(Kenkyū-buntansha) |
HAGA Tatsuya School of Medicine, University of Tokyo, Professor, 医学部, 教授 (30011646)
NOMURA Yasuyuki Faculty of Pharmaceutical Sciences, Hokkaido University, Professor, 薬学部, 教授 (00034041)
SHIMIZU Takao School of Medicine, University of Tokyo, Professor, 医学部, 教授 (80127092)
ICHIKAWA Astushi Faculty of Pharmaceutical Sciences, Kyoto University, Professor, 薬学部, 教授 (10025695)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥195,200,000 (Direct Cost: ¥195,200,000)
Fiscal Year 1995: ¥68,800,000 (Direct Cost: ¥68,800,000)
Fiscal Year 1994: ¥62,000,000 (Direct Cost: ¥62,000,000)
Fiscal Year 1993: ¥64,400,000 (Direct Cost: ¥64,400,000)
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| Keywords | GTP-binding proteins / Second messengers / Membrane receptors / Ion channels / Effectors / Phosphorylation / Signal transduction |
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| Research Abstract |
This research project was organized by ten and a couple of investigators in order to study the roles of alphabetagamma-heterotrimeric GTP-binding proteins (G proteins) in signal transduction from 1993 to 1995. The major findings obtained in this research project are summarized as follows. 1) The cDNAs of membrane-bound receptors that coupled to G proteins were cloned. Such included a novel photo-receptor, pinopsin, which may play an important role in the circadian rhythm of melatonin synthesis, and various types of prostaglandin receptors. 2) The betagamma subunits of G proteins stimulated the phosphorylation of G protein-coupled membrane receptors (GR) such as muscarinic acetylcholine receptors by GR kinases (GRKs). This receptor phosphorylation by GRKs appeared to be involved in the internalization of the phosphorylated receptor molecules. 3) Wortmannin was found to be a specific inhibitor of phosphoinositide (PI) 3-kinase. Using this specific inhibitor, PI 3-kinase was shown to be involved signal transduction pathways mediated through two different types of membrane receptors, one possessing tyrosine kinase activity and the other activating G proteins. 4) Phospholipase D activity was stimulated not only by G proteins but also by small GTP-binding proteins such as Rho and ARF.5) The Post-translational modification of G proteins, fatty-acid addition to alpha subunits, isoprenylation and phosphorylation of gamma subunits, playd important roles in the functional regulation of the signal-transducing proteins.
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