Role of PI3-kinase in Bcl-X induction and apoptosis inhibition mediated by IL-3 or IGF-1 in Baf-3 cells.
In Baf-3 cells, IL-3 and IGF-1 both inhibit cell death. These growth factors act at least on two different pathways involved in the inhibition of apoptosis. They both upregulate Bcl-X at the mRNA and protein levels and also activate a pathway which inhibits apoptosis in the absence of protein synthesis. Recently, these two growth factors have been shown to activate the PI3-kinase-AKT pathway which leads to the phosphorylation of the pro-apoptotic Bcl-XL regulator Bad. In this study, we have investigated the role of PI3-kinase in the regulation of Bcl-X expression and in the survival of Baf-3 cells. We show that PI3-kinase activation is involved in the upregulation of Bcl-X mRNA induced by both IL-3 and IGF-1. Moreover, PI3-kinase activity is also necessary for inhibition of apoptosis and caspase regulation by IGF-1 but not IL-3.
Leverrier
Y
Y
Immunologie Cellulaire, Laboratoire de Biologie Moléculaire et Cellulaire, Ecole Normale Supérieure de Lyon CNRS UMR49 INRA LA 913, 46 allée d'Italie, 69364 Lyon cedex 07, France.
Thomas
J
J
Mathieu
A L
AL
Low
W
W
Blanquier
B
B
Marvel
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein
D020169:Caspases; D004791:Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D007377:Interleukin-3; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; C494812:Bcl2l1 protein, mouse