Screening for Inhibitors of Kinase Autophosphorylation

Methods Mol Biol. 2016:1439:159-69. doi: 10.1007/978-1-4939-3673-1_10.

Abstract

Autophosphorylation of kinases influences their conformational state and can also regulate enzymatic activity. Recently, this has become an area of interest for drug discovery. Using Alk2 as an example, we present two protocols - one based on phosphate-binding Alphascreen beads, the other on coupled luminescence measurements of ADP formation - that can be used to screen for inhibitors of autophosphorylation.

Keywords: ADP-Glo; Alk2; Alphascreen; Assay development; Autoactivation; Autophosphorylation; High-throughput screening; Kinase; Luminescence.

MeSH terms

  • Activin Receptors, Type I / metabolism*
  • Adenosine Diphosphate / metabolism
  • Drug Evaluation, Preclinical / methods*
  • High-Throughput Screening Assays / methods
  • Humans
  • Luminescent Measurements / methods*
  • Phosphorylation / drug effects*
  • Recombinant Proteins / metabolism

Substances

  • Recombinant Proteins
  • Adenosine Diphosphate
  • ACVR1 protein, human
  • Activin Receptors, Type I