The ecdysone inducible gene expression system: unexpected effects of muristerone A and ponasterone A on cytokine signaling in mammalian cells.
Inducible gene expression systems in mammalian cells have been shown to be valuable processes to study the specific function of a protein in differentiation, proliferation or survival/apoptosis. Usually, these systems use as inducible reagents, compounds that are thought to be neutral and devoid of physiological or biologically undesirable effects in mammalian cells. We recently used the ecdysone inducible gene expression system in hematopoietic cells and found that the two inducer analogs of ecdysone, muristerone A and ponasterone A, altered the signaling pathways induced by IL-3 in the pro-B cell-line, Ba/F3. Indeed, we showed that these two analogs potentiate the IL-3-dependent activation of the PI 3-kinase/Akt pathway, which could ultimately interfere with the growth, and/or survival of these cells.
Constantino
S
S
Institut Cochin de Génétique Moléculaire, Institut National de la Santé et de la Recherche Médicale U. 363, Hôpital Cochin, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France.
Santos
R
R
Gisselbrecht
S
S
Gouilleux
F
F
D000818:Animals; D002460:Cell Line; D004441:Ecdysterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects*; D007377:Interleukin-3 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects*
D004441:Ecdysterone; D007377:Interleukin-3; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C055348:muristerone A; C008999:ponasterone A