| Project/Area Number |
06672169
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | University of Tokyo |
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Principal Investigator |
HAZEKI Osamu University of Tokyo Faculty of Pharmaceutical Sciences Lecturer, 薬学部, 講師 (80142751)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | PI3-KINASE / WORTMANNIN / NEUTROPHILS / CTP -BINDING PROTEIN / betagammaSUBUNITS |
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| Research Abstract |
The mechanism by which stimulation of GTP-binding protein-coupled receptors activates cellular phosphoinositide 3-kinase (PI 3-kinase) was examined. It is known that stimulation of insulin or growth factor receptors activates PI 3-kinase by producing tyrosine-phosphorylated peptide that associates with and stimulates the p85/p110 subtype of the enzyme. However, such a tyrosine-phosphorylated protein can not be found in the neutrophils stimulated by fMLP,in spite that a marked accumulation of PIP_3, a product of PI 3-kinase, can be observed in the cells. At the beginning of this study, we found the occurrence of PI 3 -kinase activity that is unaffected by tyrosine-phosphorylated proteins but is stimulated by betagamma subunits of GTP-binding proteins (Gbetagamma). Similar results were obtained by other groups and more recently one subtype of Gbetagamma-sensitive PI 3-kinase (p110gamma) was cloned. These studies seemed to indicate that GTP-binding proteins and tyrosine kinases act independently and stimulate the different subtypes of PI 3-kinase. We found later, however, that co-stimulation of cells with insulin and fMLP causes synergistic accumulation of PIP_3. We also found in cell-free systems the occurrence of PI 3-kinase that can be synergistically activated by tyrosine-phosphorylated peptide and Gbetagamma. We are now examining for a physiological role of this novel type of regulation.
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