Studies on regulation of cytoskeleton by heterotrimeric GTP-binding protein signaling.
| Project/Area Number |
14572089
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
UEDA Hiroshi Institute for Developmental Research, Aichi Human Service Center, Department of Molecular Neurobiology, Reseach Associate, 神経制御学部, 研究員 (50253779)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | G protein / Rho / Rho-kinase / Akt / protein tyrosine phosphatase / Apoptosis / cytoskeleton / cell adhesion / 三量体G蛋白質 / 細胞接着剤 / 細胞死 / インスリン |
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| Research Abstract |
We have previously reported that expression of the constitutively active mutant of G_α11 or stimulation of m1 muscarinic acetylcholine receptor induced proteolytic activation of Rho-kinase (ROCK-I) by caspase and apoptosis in HeLa cells. Insulin, a major survival factor in many cells, strongly increased phosphorylation of Akt, which was completely blocked by carbachol. This latter effect was partially inhibited by treatment with the tyrosine phosphatase inhibitors, orthovanadate and pervanadate. In parallel with these observations, carbachol attenuated insulin-stimulated tyrosine phosphorylation of IRS-1, an effect eliminated by orthovanadate. On the other hand, carbachol induced rapid stimulation of endogenous RhoA, and espression of a constitutively active mutant of RhoA increased ROCK-I cleavage. Orthovanadate and the dominant negative mutant of RhoA partially, and their combination completely, inhibited carbachol-induced ROCK-I cleavage and apoptosis. These results demonstrate that
… More
Gq/11 signaling induces apoptosis by reducing insulin-stimulated Akt phosphorylation through tyrosine dephosphorylation and activating RhoA in HeLa cells. In another study, in order to clarify the role of Gi2 in the ventricular zone of embryonic brains, we first administered pertussis toxin (PTX) into the lateral ventricle of mouse brains at embryonic day 14.5. Bromodeoxyuridine labeling revealed fewer numbers of bromodeoxyuridine-positive cells in the cerebral cortices of PTX-injected embryos, suggesting impaired proliferation of neuroepithelial cells. Next among agonists for several Gi-coupled receptors tested, endothelin most effectively stimulated the incorporation of [3H]thymidine in the presence of fibronectin, via the endothelin-B receptor in cultured neural progenitor cells. This was associated with phosphorylation of extracellular signal regulated kinase, and PTX partially inhibited both endothelin-stimulated DNA synthesis and phosphorylation of extracellular signal regulated kinase. These findings indicate that Gi2 mediates signaling from receptors such as endothelin-B receptor to maintain mitogenic activity in the neural progenitor cells of developing brain. Less
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Report
(3 results)
Research Products
(5 results)
