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A rapidly reversible chemical dimerizer system to study lipid signaling in living cells.

Authors
  • Feng, Suihan
  • Laketa, Vibor
  • Stein, Frank
  • Rutkowska, Anna
  • MacNamara, Aidan
  • Depner, Sofia
  • Klingmüller, Ursula
  • Saez-Rodriguez, Julio
  • Schultz, Carsten
Type
Published Article
Journal
Angewandte Chemie International Edition in English
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jun 23, 2014
Volume
53
Issue
26
Pages
6720–6723
Identifiers
DOI: 10.1002/anie.201402294
PMID: 24841150
Source
Medline
Keywords
License
Unknown

Abstract

Chemical dimerizers are powerful tools for non-invasive manipulation of enzyme activities in intact cells. Here we introduce the first rapidly reversible small-molecule-based dimerization system and demonstrate a sufficiently fast switch-off to determine kinetics of lipid metabolizing enzymes in living cells. We applied this new method to induce and stop phosphatidylinositol 3-kinase (PI3K) activity, allowing us to quantitatively measure the turnover of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and its downstream effectors by confocal fluorescence microscopy as well as standard biochemical methods.

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