Analysis of K-Ras Interactions by Biotin Ligase Tagging

Cancer Genomics Proteomics. 2017 Jul-Aug;14(4):225-239. doi: 10.21873/cgp.20034.

Abstract

Background: Mutations of the human K-Ras 4B (K-Ras) G protein are associated with a significant proportion of all human cancers. Despite this fact, a comprehensive analysis of K-Ras interactions is lacking. Our investigations focus on characterization of the K-Ras interaction network.

Materials and methods: We employed a biotin ligase-tagging approach, in which tagged K-Ras proteins biotinylate neighbor proteins in a proximity-dependent fashion, and proteins are identified via mass spectrometry (MS) sequencing.

Results: In transfected cells, a total of 748 biotinylated proteins were identified from cells expressing biotin ligase-tagged K-Ras variants. Significant differences were observed between membrane-associated variants and a farnesylation-defective mutant. In pancreatic cancer cells, 56 K-Ras interaction partners were identified. Most of these were cytoskeletal or plasma membrane proteins, and many have been identified previously as potential cancer biomarkers.

Conclusion: Biotin ligase tagging offers a rapid and convenient approach to the characterization of K-Ras interaction networks.

Keywords: Proximity mapping; pancreatic cancer; subcellular localization.

MeSH terms

  • Animals
  • Biotinylation
  • Carbon-Nitrogen Ligases / genetics
  • Carbon-Nitrogen Ligases / metabolism*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Mice
  • Mutation
  • NIH 3T3 Cells
  • Oncogene Protein p21(ras) / genetics
  • Oncogene Protein p21(ras) / metabolism*
  • Protein Binding
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • Escherichia coli Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Oncogene Protein p21(ras)
  • Carbon-Nitrogen Ligases
  • birA protein, E coli