Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21

Nature. 1992 Jul 23;358(6384):351-4. doi: 10.1038/358351a0.


The stimulation of a variety of cell surface receptors promotes the accumulation of the active, GTP-bound form of Ras proteins in cells. This is a critical step in signal transduction because inhibition of Ras activation by anti-Ras antibodies or dominant inhibitory Ras mutants blocks many of the effects of these receptors on cellular function. To reach the active GTP-bound state, Ras proteins must first release bound GDP. This rate-limiting step in GTP binding is thought to be catalysed by a guanine-nucleotide-releasing factor (GRF). Here we report the cloning of complementary DNAs from a rat brain library that encode a approximately 140K GRF for Ras p21 (p140Ras-GRF). Its carboxy-terminal region is similar to that of CDC25, a GRF for Saccharomyces cerevisiae RAS. This portion of Ras-GRF accelerated the release of GDP from RasH and RasN p21 in vitro, but not from the related RalA, or CDC42Hs GTP-binding proteins. A region in the amino-terminal end of Ras-GRF is similar to both the human breakpoint cluster protein, Bcr, and the dbl oncogene product, a guanine-nucleotide-releasing factor for CDC42Hs. An understanding of Ras-GRF function will enhance our knowledge of the many signal transduction pathways mediated by Ras proteins.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • Cloning, Molecular
  • DNA / genetics
  • Guanine Nucleotide Exchange Factors
  • Guanosine Diphosphate / metabolism
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Proteins / genetics*
  • Proteins / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • RNA / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Nucleic Acid
  • Signal Transduction
  • ras Guanine Nucleotide Exchange Factors
  • ras-GRF1


  • Guanine Nucleotide Exchange Factors
  • Oligodeoxyribonucleotides
  • Proteins
  • Recombinant Proteins
  • ras Guanine Nucleotide Exchange Factors
  • ras-GRF1
  • Guanosine Diphosphate
  • RNA
  • DNA
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)

Associated data

  • GENBANK/X67241