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Updated: Jan 27, 2026

Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
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Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Published on: September 20, 2011

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Caffeine inhibits PI3K and mTORC2 in Dictyostelium and differentially affects multiple other cAMP chemoattractant

A F M Tariqul Islam1, Margarethakay Scavello1,2, Pouya Lotfi1

  • 1Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.

Molecular and Cellular Biochemistry
|March 18, 2019
PubMed

Insights

Caffeine inhibits cyclic adenosine monophosphate (cAMP) synthesis in Dictyostelium by targeting phosphatidylinositol 3-kinase (PI3K) and mechanistic target of rapamycin complex 2 (mTORC2). This reveals caffeine

Area of Science:

  • Cellular signaling pathways
  • Biochemistry
  • Molecular biology

Background:

  • Caffeine is frequently used in Dictyostelium research to block cyclic adenosine monophosphate (cAMP) synthesis, preventing interference with chemoattractant-induced responses.
  • The precise mechanism by which caffeine inhibits cAMP synthesis in Dictyostelium remains largely uncharacterized.

Purpose of the Study:

  • To elucidate the molecular mechanism underlying caffeine's inhibition of cAMP synthesis in Dictyostelium.
  • To investigate the broader effects of caffeine on the cAMP chemoattractant signaling network in Dictyostelium.

Main Methods:

  • Investigated the impact of caffeine on key signaling molecules, including PI3K and mTORC2.
  • Analyzed the effects of caffeine on downstream signaling components like RasG, Rap1, PKA, cGMP, MyoII, ERK1, and F-actin.
  • Utilized Dictyostelium as a model organism to study chemoattractant signaling.

Main Results:

  • Caffeine was found to inhibit both phosphatidylinositol 3-kinase (PI3K) and mechanistic target of rapamycin complex 2 (mTORC2).
  • Both PI3K and mTORC2 were identified as crucial for chemoattractant-stimulated cAMP production, explaining caffeine's inhibitory effect.
  • Caffeine treatment resulted in increased cAMP-induced RasG and Rap1 activation, alongside inhibition of PKA, cGMP, MyoII, and ERK1 responses.
  • Observed variable effects of caffeine on F-actin and ERK2, dependent on the specific assay and Dictyostelium strain.

Conclusions:

  • Caffeine significantly impacts cAMP-induced chemotactic signaling pathways in Dictyostelium.
  • The inhibitory action of caffeine likely involves multiple targets, prominently including PI3K and mTORC2.
  • This study provides a mechanistic understanding of caffeine's role in modulating cellular signaling in Dictyostelium.
Keywords:
CaffeineChemotaxisDictyosteliumPI3KcAMPmTORC2

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