Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase

Chem Biol. 2005 Jan;12(1):99-107. doi: 10.1016/j.chembiol.2004.11.009.

Abstract

Polo-like kinases (PLKs) play critical roles throughout mitosis. Here, we report that wortmannin, which was previously thought to be a highly selective inhibitor of phosphoinositide (PI) 3-kinases, is a potent inhibitor of mammalian PLK1. Observation of the wortmannin-PLK1 interaction was enabled by a tetramethylrhodamine-wortmannin conjugate (AX7503) that permits rapid detection of PLK1 activity and expression in complex proteomes. Importantly, we show that wortmannin inhibits PLK1 activity in an in vitro kinase assay with an IC(50) of 24 nM and when incubated with intact cells. Taken together, our results indicate that, at the concentrations of wortmannin commonly used to inhibit PI 3-kinases, PLK1 is also significantly inhibited.

Publication types

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

MeSH terms

  • Androstadienes / pharmacology*
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Jurkat Cells
  • Molecular Conformation
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Rhodamines / chemical synthesis
  • Rhodamines / chemistry
  • Rhodamines / pharmacology
  • Wortmannin

Substances

  • AX 7503
  • Androstadienes
  • Cell Cycle Proteins
  • Heterocyclic Compounds, 4 or More Rings
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Rhodamines
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • Wortmannin