Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2

Science. 1993 May 28;260(5112):1338-43. doi: 10.1126/science.8493579.

Abstract

A human complementary DNA was isolated that encodes a widely expressed protein, hSos1, that is closely related to Sos, the product of the Drosophila son of sevenless gene. The hSos1 protein contains a region of significant sequence similarity to CDC25, a guanine nucleotide exchange factor for Ras from yeast. A fragment of hSos1 encoding the CDC25-related domain complemented loss of CDC25 function in yeast. This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. Mammalian cells overexpressing full-length hSos1 had increased guanine nucleotide exchange activity. Thus hSos1 is a guanine nucleotide exchange factor for Ras. The hSos1 interacted with growth factor receptor-bound protein 2 (GRB2) in vivo and in vitro. This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Cycle Proteins*
  • Cell Line
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism*
  • GRB2 Adaptor Protein
  • Guanine Nucleotide Exchange Factors
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Proteins / metabolism*
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Son of Sevenless Proteins
  • ras Guanine Nucleotide Exchange Factors
  • ras-GRF1*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Fungal Proteins
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • Grb2 protein, mouse
  • Guanine Nucleotide Exchange Factors
  • Membrane Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • Son of Sevenless Proteins
  • ras Guanine Nucleotide Exchange Factors
  • ras-GRF1
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)