Biological properties of human c-Ha-ras1 genes mutated at codon 12 View Full Text


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Article Info

DATE

1984-11

AUTHORS

Peter H. Seeburg, Wendy W. Colby, Daniel J. Capon, David V. Goeddel, Arthur D. Levinson

ABSTRACT

Vertebrate genomes contain proto-oncogenes whose enhanced expression or alteration by mutation seems to be involved in the development of naturally occurring tumours1,2. These activated genes, usually assayed by their ability to induce the malignant transformation of NIH 3T3 cells, are frequently related to the ras oncogene3–10 of Harvey (Ha-ras)11 or Kirsten (Ki-ras)12 murine sarcoma viruses, or a third member of this family (N-ras)13–15. Activation involves point mutation which often affect codon 12 (refs 16–26) of the encoded 21,000-molecular weight polypeptide (p21). To provide insight into structural requirements involved in p21 activation, we have now constructed 20 mutant c-Ha-ras1 genes by in vitro mutagenesis, each encoding a different amino acid at codon 12. Analysis of rat fibroblasts transfected with these altered genes demonstrates that all amino acids except glycine (which is encoded by normal cellular ras genes) and proline at position 12 activate p21, suggesting a requirement for an α-helical structure in this region of the polypeptide. The morphological phenotype of cells transformed by the activated genes can, however, depend on the particular amino acid at this position. More... »

PAGES

71-75

References to SciGraph publications

  • 1982-11. Mechanism of activation of a human oncogene in NATURE
  • 1982-07. T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes in NATURE
  • 1983-12. Induction of mammary carcinomas in rats by nitroso-methylurea involves malignant activation of H-ras-1 locus by single point mutations in NATURE
  • 1982-11. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene in NATURE
  • 1982-12. Oncogenes in solid human tumours in NATURE
  • 1983-08. Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations in NATURE
  • 1983-08. Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1 in NATURE
  • 1982-06. Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene in NATURE
  • 1983-06. Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1 in NATURE
  • 1983-03. Characterization of a human colon/lung carcinoma oncogene in NATURE
  • 1984-08. Comparative biochemical properties of normal and activated human ras p21 protein in NATURE
  • 1982-06. Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus in NATURE
  • 1982-12. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change in NATURE
  • 1970-08. Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 in NATURE
  • 1983-03. Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue in NATURE
  • 1984-05. Ha-ras oncogenes are activated by somatic alterations in human urinary tract tumours in NATURE
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    http://scigraph.springernature.com/pub.10.1038/312071a0

    DOI

    http://dx.doi.org/10.1038/312071a0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1017595713

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/6092966


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