The effector loop and prenylation site of R-Ras are involved in the regulation of integrin function

Oncogene. 2000 Oct 12;19(43):4961-9. doi: 10.1038/sj.onc.1203876.


The closely related small GTP-binding proteins H-Ras and R-Ras have opposing effects on the regulation of integrin cell adhesion receptors. To gain insight into the properties of R-Ras with respect to the regulation of integrin function and interactions with downstream effectors we performed an analysis of R-Ras variants containing mutations in the effector binding domain and C-terminal prenylation site. We found that the activation of the downstream effector PI 3-kinase was sensitive to mutations in the effector binding domain, as was the binding to the effectors, Ral-GDS, Raf-1 and the novel effector Nore1. Furthermore, specific mutations in the effector binding loop and C-terminal prenylation motif impaired the ability of R-Ras to regulate integrin function in CHO cells. However, the ability of the R-Ras effector loop mutants to bind, and activate known effectors did not correlate with their ability to regulate integrin function. Thus, the known R-Ras effectors are not critical for regulating integrin activation, at least in CHO cells. Consequently, these studies provide insight into the structural basis of the interactions between R-Ras and its candidate effectors and suggest the existence of novel mechanisms through which this GTPase could regulate cell adhesion.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CHO Cells / metabolism
  • Catalytic Domain
  • Cell Membrane / metabolism
  • Conserved Sequence
  • Cricetinae
  • Enzyme Activation
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • GTP Phosphohydrolases / physiology*
  • Integrins / physiology*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Binding
  • Protein Prenylation
  • Proto-Oncogene Proteins c-raf / metabolism
  • Signal Transduction / physiology*
  • ral Guanine Nucleotide Exchange Factor / metabolism
  • ras Proteins / genetics
  • ras Proteins / metabolism
  • ras Proteins / physiology*


  • Integrins
  • ral Guanine Nucleotide Exchange Factor
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-raf
  • GTP Phosphohydrolases
  • ras Proteins