Measurement of KRAS-GTPase Activity

Methods Mol Biol. 2024:2797:91-102. doi: 10.1007/978-1-0716-3822-4_7.

Abstract

Oncogenic mutations in KRAS typically impact the GAP-mediated and intrinsic GTP hydrolysis activity resulting in elevated levels of cellular KRAS-GTP. The development of biochemical assays for GTPase activity provides an opportunity to quantitatively measure the impact of these mutations on GTP hydrolysis. Here we describe a biochemical assay that measures the release of free phosphate upon hydrolysis of the GTP nucleotide and allows the measurement of intrinsic or GAP-stimulated GTP hydrolysis by KRAS. This assay can be used to measure GTPase activity under single turnover conditions.

Keywords: Free phosphate; GAP; GTPase activity; Kinetic measurement; NF1; Phosphate sensor; RAS; RASA1.

MeSH terms

  • GTPase-Activating Proteins* / metabolism
  • Guanosine Triphosphate
  • Hydrolysis
  • Kinetics
  • Mutation
  • Proto-Oncogene Proteins p21(ras)* / genetics

Substances

  • Proto-Oncogene Proteins p21(ras)
  • Guanosine Triphosphate
  • GTPase-Activating Proteins