The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21

Cell. 1990 Nov 16;63(4):843-9. doi: 10.1016/0092-8674(90)90150-d.


The neurofibromatosis type 1 (NF1) protein contains a region of significant sequence similarity to ras p21 GTPase-activating protein (GAP) and the yeast IRA1 gene product. A fragment of NF1 cDNA encoding the GAP-related domain (NF1 GRD) was expressed, immunoaffinity purified, and assayed for effects on N-ras p21 GTPase activity. The GTPase of wild-type ras p21 was stimulated by NF1 GRD, but oncogenic mutants of ras p21 (Asp-12 and Val-12) were unaffected, and the GTPase of an effector mutant (Ala-38) was only weakly stimulated. NF1 GRD also down-regulated RAS function in S. cerevisiae. The affinity of NF1 GRD for ras p21 was estimated to be 250 nM: this is more than 20-fold higher than the affinity of GAP for ras p21. However, its specific activity was about 30 times lower. These kinetic measurements suggest that NF1 may be a significant regulator of ras p21 activity, particularly at low ras p21 concentrations.

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
  • Binding, Competitive
  • Cloning, Molecular
  • GTP Phosphohydrolases / metabolism*
  • GTPase-Activating Proteins
  • Guanylyl Imidodiphosphate / metabolism
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Neurofibromatosis 1 / genetics*
  • Neurofibromin 1
  • Oligonucleotide Probes
  • Oncogene Protein p21(ras) / metabolism*
  • Proteins / genetics*
  • Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Transfection
  • ras GTPase-Activating Proteins


  • GTPase-Activating Proteins
  • Neurofibromin 1
  • Oligonucleotide Probes
  • Proteins
  • ras GTPase-Activating Proteins
  • Guanylyl Imidodiphosphate
  • GTP Phosphohydrolases
  • Oncogene Protein p21(ras)

Associated data

  • GENBANK/M61213