| Project/Area Number |
04304048
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | The Institute of Physical and Chemical Research (RIKEN) (1993)
The University of Tokyo (1992) |
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Principal Investigator |
UI Michio The Institute of Physical and Chemical Research, Researcher, 宇井特別研究室, 特別招聘研究員 (50001037)
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| Co-Investigator(Kenkyū-buntansha) |
OKAJIMA Fumikazu Institute of Endocrinology, Associate Professor, 内分泌研究所, 助教授 (30142748)
HAGA Tatsuya Faculty of Medicine, University of Tokyo, Professor, 医学部, 教授 (30011646)
ICHIKAWA Atsushi Faculty of PHamaceutical Sciences, Kyoto University, Professor, 薬学部, 教授 (10025695)
NOZAWA Yoshinori Medical School, Gifu University, Professor, 医学部, 教授 (10021362)
KATADA Toshiaki Faculty of Pharmaceutical Sciences, University of Tokyo, Professorr, 薬学部, 教授 (10088859)
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| Project Period (FY) |
1992 – 1993
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| Keywords | heterotrimeric G proteins / cell differentiation / protein tyrosine phosphorylation / wortmannin / PI-3-kinase / phospholipase / betagamma-subunit of G protein / receptor kinase |
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| Research Abstract |
PI 3-kinase, which is activated by phosphotyrosines through its binding via the SH2 domain, was found to play an essential role in G protein-mediated signaling systems (M.Ui). This finding was achieved with the use of a novel inhibitor of this enzyme, wortmannin, and is the first to show involvement of G proteins in the tyrosine phosphorylation system that has been so far considered to be triggerred by stimulation of growth factor (or cell adhesion) receptors without mediation of G proteins. An additional role of G proteins was shown by T.Kataca in differentiation of HL-60 cells in response to autocrine factors released by treatment of the cells with retinoic acid. Similar role of G proteins was found by U.Nomura in differentiation of neuronal cells as a mechanism of synapse plasticity. Coupling mechanisms for receptorp-G protein-phospholipase has been studied extensively by Y.Nozawa, F.Okajima and N.Nakahata who analyzed activation of phosphlipases C and D, in hibitino of phospholipase C and purinergic receptor-mediated activation or phospholipse A_2, respectively. Molecular mechanisms of the coupling were the subject of A Ichikawa and T.Haga. Ichikawa purified three isoforms of prostaglandin E receptors, succeeded in cDNA cloning and sequencing of amino acids, and identified G proteins specifically coupled to these receptors. Haga found a physiological role of betaganmma-subunit of G proteins as an inhibitor of G protein-coupled receptor kinase which contributed to desensitization of signal reception. Isomeric forms of the betagamma were analyzed by T.Asano who purified and cloned these isomers providing evidence for their functional differences. N.Kimura continued his original work on the role of NDP kinase as a physiological regulator of G proteins. Thus, thjis research group has made great contributions to current understanding of cellular and molecular mechanisms for receptorp-G protein-effector coupling.
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