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

A. F.M. Tariqul Islam, Margarethakay Scavello, Pouya Lotfi, Dustin Daniel, Pearce Haldeman, Pascale G Charest

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Caffeine is commonly used in Dictyostelium to inhibit the synthesis of the chemoattractant cAMP and, therefore, its secretion and the autocrine stimulation of cells, in order to prevent its interference with the study of chemoattractant-induced responses. However, the mechanism through which caffeine inhibits cAMP synthesis in Dictyostelium has not been characterized. Here, we report the effects of caffeine on the cAMP chemoattractant signaling network. We found that caffeine inhibits phosphatidylinositol 3-kinase (PI3K) and mechanistic target of rapamycin complex 2 (mTORC2). Both PI3K and mTORC2 are essential for the chemoattractant-stimulated cAMP production, thereby providing a mechanism for the caffeine-mediated inhibition of cAMP synthesis. Our results also reveal that caffeine treatment of cells leads to an increase in cAMP-induced RasG and Rap1 activation, and inhibition of the PKA, cGMP, MyoII, and ERK1 responses. Finally, we observed that caffeine has opposite effects on F-actin and ERK2 depending on the assay and Dictyostelium strain used, respectively. Altogether, our findings reveal that caffeine considerably affects the cAMP-induced chemotactic signaling pathways in Dictyostelium, most likely acting through multiple targets that include PI3K and mTORC2.

Original languageEnglish (US)
JournalMolecular and Cellular Biochemistry
DOIs
StatePublished - Jan 1 2019

Fingerprint

Phosphatidylinositol 3-Kinase
Dictyostelium
Chemotactic Factors
Caffeine
TOR complex 2
Actins
Assays
Chemical activation
Cells

Keywords

  • Caffeine
  • cAMP
  • Chemotaxis
  • Dictyostelium
  • mTORC2
  • PI3K

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Caffeine inhibits PI3K and mTORC2 in Dictyostelium and differentially affects multiple other cAMP chemoattractant signaling effectors. / Tariqul Islam, A. F.M.; Scavello, Margarethakay; Lotfi, Pouya; Daniel, Dustin; Haldeman, Pearce; Charest, Pascale G.

In: Molecular and Cellular Biochemistry, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Tariqul Islam, A. F.M.

AU - Scavello, Margarethakay

AU - Lotfi, Pouya

AU - Daniel, Dustin

AU - Haldeman, Pearce

AU - Charest, Pascale G

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