Biological and biochemical properties of human rasH genes mutated at codon 61

Cell. 1986 Jan 17;44(1):167-76. doi: 10.1016/0092-8674(86)90495-2.


Using site-directed mutagenesis, we have introduced mutations encoding 17 different amino acids at codon 61 of the human rasH gene. Fifteen of these substitutions increased rasH transforming activity. The remaining two mutants, encoding proline and glutamic acid, displayed transforming activities similar to the normal gene. Overall, these mutants vary over 1000-fold in transforming potency. Increased levels of p21 expression were required for transformation by weakly transforming mutants. The mutant proteins were unaltered in guanine nucleotide binding properties. However, all 17 different mutant proteins displayed equivalently reduced rates of GTP hydrolysis, 8- to 10-fold lower than the normal protein. There was no quantitative correlation between reduction in GTPase activity and transformation, indicating that reduced GTP hydrolysis is not sufficient to activate ras transforming potential.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Transformation, Neoplastic / etiology*
  • Fibroblasts
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • GTP Phosphohydrolases / physiology
  • Gene Expression Regulation
  • Guanosine Triphosphate / metabolism
  • Humans
  • Mice
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / physiology
  • Protein Conformation
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogenes*
  • Transfection


  • Neoplasm Proteins
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)