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2003 Fiscal Year Final Research Report Summary

Regulation of cytoskeletons by heterotrimeric GTP-binding proteins

Research Project

Project/Area Number 14580663
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionInstitute for Developmental Research, Aichi Human Service Center

Principal Investigator

ASANO Tomiko  Institute for Developmental Research, Aichi Human Service Center, Department of Molecular Neurobiology, Department Head, 神経制御学部, 部長 (70100154)

Project Period (FY) 2002 – 2003
KeywordsG protein / Rho / Apoptosis / Akt / Protein tyrosine phosphatase / Endothelin / Fibronectin / Neural progenitor cells
Research Abstract

In this study, we investigate the molecular mechanisms of Gαq/11-induced apoptosis in m1 muscarinic acetylcholine receptor-expressing HeLa cells. Overexpression of the constitutively active mutant of Akt inhibited carbachol-induced ROCK-I cleavage. 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 inhibitor, orthovanadate. In parallel with these observations, carbachol attenuated insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1, an effect eliminated by orthovanadate. On the other hand, carbachol induced rapid stimulation of endogenous RhoA, and expression 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 … More demonstrate that Ga/11 signaling induces apoptosis by reducing insulin-stimulated Akt phosphorylation through tyrosine dephosphorylation and activating RhoA in HeLa cells.
In order to clarify the role of Gi2 in the ventricular zone of embryonic brains, we administered pertussis toxin (PTX) into the lateral ventricle of mouse brains at E14.5. Examination at E18.5 revealed that PTX decreased total cells and bromodeoxyuridine-positive cells in the cerebral cortices, suggesting impaired proliferation of neuroepithelial cells. Then we cultured neural progenitor cells from rat embryonic brains and evaluated the mitogenic effects of agonists for several Gi-coupled receptors, which are known to be expressed in the ventricular zone. Among agonists tested, endothelin most effectively stimulated the incorporation of [^3H]thymidine in the presence of fibronectin, via the endothelin-B receptor. This was associated with phosphorylation of ERK, and PTX partially inhibited both endothelin-stimulated DNA synthesis and phosphorylation of ERK. These findings indicated that Gi2 mediates signaling from receptors such as endothelin-B receptor to maintain mitogenic activity in the neural progenitor cells of developing brain. Less

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Abe, M.: "Goniodomin A, an antifungal polyether macrolide, exhibits antiangiogenic activities via inhibition of actin reorganization in endothelial cells."J.Cell.Physiol.. 190. 109-116 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katoh-Semba, R.: "Riluzole enhances expression of brain-derived neurotrophic factor with consequence proliferation of granule precursor cells in the rat hippocampus"FASEB J.. 16(on line# 10.1096/fj.02-0143fje). 1328-1330 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Abe, M.: "Goniodomin A, an antifungal polyther macrolide, exhibits antiangiogenic activities via inhibition of actin reorganization in endothelial cells."J.Cell.Physiol. 190(1). 109-116 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katoh-Semba, R.: "Riluzole enhanced expression of brain-derived neurotrophic factor with consequence proliferation of granule precursor cells in the rat hippocampus."FASEB J.(on line#10.1096/fj.02-0143fje). 16(10). 1328-1330 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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