Multiple Ras functions can contribute to mammalian cell transformation

Cell. 1995 Feb 24;80(4):533-41. doi: 10.1016/0092-8674(95)90507-3.

Abstract

We have developed a generalized approach, using two hybrid interactions, to isolate Ha-Ras effector loop mutations that separate the ability of Ha-Ras to interact with different downstream effectors. These mutations attenuate or eliminate Ha-ras(G12V) transformation of mammalian cells, but retain complementary activity, as demonstrated by synergistic induction of foci of growth-transformed cells, and by the ability to activate different downstream components. The transformation defect of Ha-ras(G12V, E37G) is rescued by a mutant, raf1, that restores interaction. These results indicate that multiple cellular components, including Raf1, are activated by Ha-Ras and contribute to Ha-Ras-induced mammalian cell transformation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics*
  • Cells, Cultured
  • Chloramphenicol O-Acetyltransferase / analysis
  • Gene Library
  • Genes, ras / genetics*
  • Genetic Complementation Test
  • Humans
  • Mice
  • Mutation
  • Protein Kinases / analysis
  • Protein-Serine-Threonine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-raf
  • Rats
  • Recombinant Fusion Proteins / biosynthesis
  • Saccharomyces cerevisiae / genetics
  • Schizosaccharomyces / genetics
  • Transfection

Substances

  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Chloramphenicol O-Acetyltransferase
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf