Leverrier Y, Thomas J, Mathieu A L, Low W, Blanquier B, Marvel J
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.
Cell Death Differ. 1999 Mar;6(3):290-6. doi: 10.1038/sj.cdd.4400492.
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.
在Baf-3细胞中，白细胞介素-3（IL-3）和胰岛素样生长因子-1（IGF-1）均能抑制细胞死亡。这些生长因子至少作用于两条参与抑制细胞凋亡的不同途径。它们在mRNA和蛋白质水平上均上调Bcl-X，并且还激活一条在无蛋白质合成情况下抑制细胞凋亡的途径。最近，已证明这两种生长因子可激活磷脂酰肌醇-3激酶-蛋白激酶B（PI3-激酶-AKT）途径，该途径导致促凋亡的Bcl-XL调节因子Bad发生磷酸化。在本研究中，我们研究了PI3-激酶在调节Bcl-X表达及Baf-3细胞存活中的作用。我们发现，PI3-激酶激活参与了由IL-3和IGF-1诱导的Bcl-X mRNA上调。此外，PI3-激酶活性对于IGF-1而非IL-3抑制细胞凋亡及半胱天冬酶调节也是必需的。
