Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos

Science. 1998 Jan 23;279(5350):560-3. doi: 10.1126/science.279.5350.560.

Abstract

The Son of Sevenless (Sos) proteins control receptor-mediated activation of Ras by catalyzing the exchange of guanosine diphosphate for guanosine triphosphate on Ras. The NH2-terminal region of Sos contains a Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain. In COS-1 cells, the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo. The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras. Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. These results reveal a potential mechanism for coupling of Ras and Rac signaling pathways.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cell Membrane / ultrastructure
  • Enzyme Activation
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / metabolism*
  • Guanine Nucleotide Exchange Factors
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mitogen-Activated Protein Kinases*
  • Proteins / metabolism
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins / metabolism
  • Retroviridae Proteins, Oncogenic / chemistry
  • Signal Transduction
  • Son of Sevenless Proteins
  • Transfection
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • ras Guanine Nucleotide Exchange Factors
  • ras Proteins / metabolism*

Substances

  • Actins
  • Cell Cycle Proteins
  • Guanine Nucleotide Exchange Factors
  • MCF2 protein, human
  • Membrane Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Retroviridae Proteins, Oncogenic
  • Son of Sevenless Proteins
  • ras Guanine Nucleotide Exchange Factors
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • ras Proteins