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Protein kinase C-mediated bidirectional regulation of endothelial cell growth

Research Project

Project/Area Number 05670039
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General physiology
Research InstitutionUniversity of Tokyo

Principal Investigator

TAKUWA Noriko  University of Tokyo, Faculty of Medicine, Department of Physiology, Research Associate, 医学部(医), 助手 (70150290)

Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsCell cycle / Protein kinase C / Cyclin-dependent kinase / Endothelial cell
Research Abstract

In human umbilical vein endothelial cells, the protein kinase C (PKC) stimulation during the early G1 phase leads to potentiations in growth factor-stimulated DNA synthesis, the activation of cdc2 and cdk2 cyclin-dependent kinases, and the mRNA expression of cdc2, cyclins A,D1 and E,but not cdk2 or cdk4. Conversely, the PKC stimulation in the late G1 phase completely inhibits DNA synthesis, the activation of cyclin-dependent kinases, and the mRNA expression of the same set of molecules except cyclin D1. Further, we found that the PKC stimulation bimodally regulates the message levels of E2F1 and B-myb, which are transcription factors implicated in the control of the mammalian cell cycle progression. These results indicate that the PKC signal transduction pathway, depending on the timing of activation in the G1 phase, either positively or negatively regulates the message level of growth-regulating genes that are crucial for the G1 to S phase progression.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] N. Takuwa, W. Zhou, and Y. Takuwa: "Calcium, calmodulin, and cell cycle progression." Cellular Signalling. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J. Abe, W. Zhou, N. Takuwa, J. Taguchi, K. Kurokawa, M. Kuwada, and Y. Takuwa: "A fiwagillin cerivative ang : ogenesis inhibitor, AGM-1470,inhibits activation of cyclin-dependent kinases and phospharylation of retiooblastana gone producut but net protein tyrosil phosphorylatint or pro tocncogene expression in vascular endotherial cells" Cancer Res.54. 3407-3412 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] W. Zhou, N. Takuwa, M. Kumada, and Y. Takuwa: "E2F1, B-wyb and selective members of cyclin/cdk subunits are targets for protein kinase C-wediated bimodal growth regulation in vascular endothelial cells." Biochem. Biophys. Res. Cannun.199. 191-198 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J. Abe, W. Zhou, J. Taguchi, N. Takuwa, K. Miki, H. Okazaki, K. Kurokawa, M. Kumada, and Y. Takuwa: "Suppression of neointiwal smooth muscle cell accumulation in viro by antisense cdo2 and cdk2 oligonucleotioles in rat carotia artery." Biochew. Biopys. Res. Commun. 198. 16-24 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] W. Zhou, N. Takuwa, M. Kumada, and Y. Takuwa: "Protein kinase C-mediated bidirectional regulation of DNA synthesis, RB protein phosphorylation, an cyslin-dependent kinase in numan vascular endothelial cells." J. Biol. Chem.268. 23041-23048 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N. Takuwa, W. Zhou, M. Kumada, and Y. Takuwa: "Ca^<2+>-dependent stimulation of retinoblastowa gene product phosphylation and p34 cdc2 kinase activation inserum-stimulated numan fibroblasts." J. Biol. Chem.268. 138-145 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Takuwa, W.Zhou, and Y.Takuwa: "Calcium, calmodulin, and cell cycle progression." Cellular Signalling. (In press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Abe, W.Zhou, N.Takuwa, J.Taguchi, K.Kurokawa, M.Kumada, and Y.Takuwa: "A fumagillin derivative angiogenesis inhibitor, AGM-1470, inhibits activation of cyclin-dependent kinases and phosphorylation of retinoblastoma gene product but not protein tyrosyl phosphorylation or protooncogene expression in vascular endothelial cells." Cancer Res.54. 3407-3412 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] W.Zhou, N.Takuwa, M.Kumada, and T.Takuwa: "E2F1, B-myb and selective members of cyclin/cdk subunits are targets for protein kinase C-mediated bimodal growth regulation in vascular endothelial cells." Biochem.Biophys.Res.Commun.199. 191-198 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Abe, W.Zhou, J.Taguchi, N.Takuwa, K,Miki, H.Okazaki, K.Kurokawa, M.Kumada, and Y.Takuwa: "Suppression of neointimal smooth muscle cell accumulation in vivo by antisense cdc2 and cdk2 oligonucleotides in rat carotid artery." Biochem.Biophys.Res.Commun.198. 16-24 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] W.Zhou, N.Takuwa, M.Kumada, and Y.Takuwa: "Protein kinase C-mediated bidirectional regulation of DNA synthesis, RB protein phosphorylation, and cyclin-dependent kinases in human vascular endothelial cells." J.Biol.Chem.268. 23041-23048 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Takuwa, W.Zhou, M.Kumada, and Y.Takuwa: "Ca^<2+>-dependent stimulation of retinoblastoma gene product phosphorylation and p34cdc2 kinase activation in serum-stimulated human fibroblasts." J.Biol.Chem.268. 138-145 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Takuwa,W.Zhou,and Y.Takuwa.: "Calcium,Calmodulin,and cell cycle progression." Cellular Signalling. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] J.Abe,W,Zhou,N.Takuwa,J.Taguchi,K.Kurokawa,M.Kumada,and Y.Takuwa: "A fumagillin derivative angiogenesis inhibitor,AGM-1470,inhibits activation of cyclin-dependent kinases and phosphorylation of retinoblastoma gene product but not protein tyrosyl phosphorylation of protooncogene expression in vascular endotherial cells." Cancer Res.54. 3407-3412 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] W.Zhou,N.Takuwa,M.Kumada,and Y.Takuwa: "E2F1,B-myb and selective members of cyclin/cdk subunits are targets for protein kinase C-mediated bimodal growth regulation in vascular endothelial cells." Biochem.Biophys.Res.Commun.199. 191-198 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] J.Abe,W.Zhou,J.Taguchi,N.Takuwa,K.Miki,H.Okazaki,K.Kurokawa,M.Kumada,and Y.Takuwa: "Suppression of neointimal smooth muscle cell accumulation in vivo by antisense cdc2 and cdk2 oligonucleotioles in rat carotid artery." Biochem.Biophys.Res.Commun.198. 16-24 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] W.Zhou,N.Takuwa,M.Kumada,and Y.Takuwa: "Protein kinase C-mediated bidirectional regulation of DNA synthesis,RB protein phosphorylation,and cyclin-dependent kinase in human vascular endothelial cells." J.Biol.Chem.268. 23041-23048 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.Takuwa,W.Zhou,M.Kumada,and Y.Takuwa: "Ca^<2+>-dependent stimulation of retinoblastoma gene product phosphorylation and p34^<cdc2>kinase activation inserum stimulated human fibroblasts." J.Biol.Chem.268. 138-145 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Zhou,Wei,et al.: "Protein kinase C-mediated bidirectional regulation of DNA synthesis,RB protein phospharylation,and cyclin-dependent kinases in human vascular endothelial cells" J.Biol.Chem.268. 23041-23048 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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