Structure/Function Studies of the ras Protein

  1. I.S. Sigal,
  2. M.S. Marshall,
  3. M.D. Schaber,
  4. U.S. Vogel,
  5. E.M. Scolnick, and
  6. J.B. Gibbs
  1. Department of Molecular Biology, Merck, Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486

This extract was created in the absence of an abstract.

Excerpt

The first ras genes were discovered as the transforming genes of murine sarcoma viruses Harvey (Ha) and Kirsten (Ellis et al. 1982; Barbacid 1987). These genes encode homologous proteins with a molecular weight of 21,000 (p21), which differ from normal cellular homologs by having amino acid substitutions at positions 12 and 59. Mutated forms of the Harvey and Kirsten ras genes as well as that of a third homologous gene, N-ras, were also isolated as transforming genes by DNA transfection experiments using DNA isolated from various human tumors. These oncogenic genes encoded p21 proteins that differed from their normal cellular homologs by having substitutions at positions 12, 13, 61, and 63. The oncogenic or activated forms of ras p21 can transform mammalian cells when expressed at normal levels. In contrast, high levels of expression of normal ras p21 are necessary for the transformation of mammalian cells. The mammalian ras genes...

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