Morphology of Ras- Transformed Cells Becomes Apparently Normal Again with Tyrosine Kinase Inhibitors without a Decrease in the Ras- GTP Complex^1

  • KWON Ho Jeong
    Department of Biotechnology The University of Tokyo
  • YOSHIDA Minoru
    Department of Biotechnology The University of Tokyo
  • MUROYA Kenkoh
    Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry
  • HATTORI Seisuke
    Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry
  • NISHIDA Eisuke
    Department of Genetics and Molecular Biology, Institute for Virus Research, Kyoto University
  • FUKUI Yasuhisa
    Department of Applied Biological Chemistry The University of Tokyo
  • BEPPU Teruhiko
    Department of Biotechnology The University of Tokyo
  • HORINOUCHI Sueharu
    Department of Biotechnology The University of Tokyo

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Radicicol, an inhibitor of protein-tyrosine kinase, was found to cause morphological reversion of v-Ha-ras-transformed NIH3T3 fibroblasts and T24 human urinary bladder carcinoma cells that contain an activated ras mutation. The network of actin stress fibers was restored during the treatment with radicicol. A similar morphological change was observed with another protein-tyrosine kinase inhibitor, herbimycin A. Radicicol did not cause any changes in the proportion of the active GTP binding form of p21ras or, its subcellular localization. These results rule out the possibility that the morphological reversion by radicicol is due to direct or indirect inhibition of the p21ras function. Cycloheximide and actinomycin D inhibited the morphological change by radicicol, suggesting that the induced transcription of a gene (s) followed by de novo protein synthesis is required for suppression of the transformed phenotype in ras-transformed cells by tyrosine kinase inhibitors.

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