IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

Dumon, Stéphanie; Santos, Susana Constantino Rosa; Debierre‐Grockiego, Françoise; Gouilleux-Gruart, Valérie; Cocault, L; Boucheron, Christine; Mollat, Patrick; Gisselbrecht, Sylvie; Gouilleux, Fabrice

doi:10.1038/sj.onc.1202796

Cited by 146 publications

(131 citation statements)

References 68 publications

(53 reference statements)

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“…We recently found that expression of a dominant negative form of STAT5 (STAT5AD749) increased the susceptibility of Ba/F3 cells to undergo apoptosis after IL-3 withdrawal. We also showed that regulation of Bcl-x gene expression by IL-3 in Ba/F3 cells is dependent on STAT5 (Dumon et al, 1999). In the present report, we provided evidence that individual inhibition of STAT5 transcriptional activity, PI 3-kinase/Akt and MEK/ MAPK pathways did not or weakly a ected the survival of Ba/F3 cells in presence of IL-3.…”

Section: Introductionsupporting

confidence: 66%

“…The role of STAT5 in the cytokine mediated suppression of apoptosis has been also documented. STAT5 promotes the IL-3 and IL-2 dependent survival of di erent hematopoietic cell lines and constitutive STAT5 activity has been observed in a T Lymphoma cell line treated with an anti-apoptotic reagent (Dumon et al, 1999;Zamorano et al, 1998;Rui et al, 1998). We recently found that expression of a dominant negative form of STAT5 (STAT5AD749) increased the susceptibility of Ba/F3 cells to undergo apoptosis after IL-3 withdrawal.…”

Section: Introductionmentioning

confidence: 92%

“…The use of cytokine receptor mutants or dominant negative/constitutively active forms of components of these signaling pathways identi®es the phosphatidylinisitol 3-kinase (PI 3-kinase)/Akt, Ras/NFIL3, Ras/Raf/ MAP kinase (MAPK) and JAK/STAT pathways as crucial regulators of survival and/or proliferation of hematopoietic cells (Songyang et al, 1997;Kuribara et al, 1999;Kinoshita et al, 1997;Liu et al, 1997;Dumon et al, 1999). Coordinated activation of these signaling pathways is commonly induced by most cytokines.…”

Section: Introductionmentioning

confidence: 99%

“…The PI 3-kinase activates the protein kinase Akt which phosphorylates Bad, thereby inhibiting its pro-apoptotic activity (del Peso et al, 1997;Zha et al, 1996). Ras/ MAPK and JAK/STAT pathways have also been shown to be required for the regulation of Bcl-2 and Bcl-x expression (Kinoshita et al, 1995;Dumon et al, 1999;Sakai et al, 1997;Leverrier et al, 1997;Fujio et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Cooperation between STAT5 and phosphatidylinositol 3-kinase in the IL-3-dependent survival of a bone marrow derived cell line

et al. 2000

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Cytokine-dependent activation of distinct signaling pathways is a common scheme thought to be required for the subsequent programmation into cell proliferation and survival. The PI 3-kinase/Akt, Ras/MAP kinase, Ras/ NFIL3 and JAK/STAT pathways have been shown to participate in cytokine mediated suppression of apoptosis in various cell types. However the relative importance of these signaling pathways seems to depend on the cellular context. In several cases, individual inhibition of each pathway is not su cient to completely abrogate cytokine mediated cell survival suggesting that cooperation between these pathways is required. Here we showed that individual inhibition of STAT5, PI 3-kinase or MEK activities did not or weakly a ected the IL-3 dependent survival of the bone marrow derived Ba/F3 cell line. However, the simultaneous inhibition of STAT5 and PI 3-kinase activities but not that of STAT5 and MEK reduced the IL-3 dependent survival of Ba/F3. Analysis of the expression of the Bcl-2 members indicated that phosphorylation of Bad and Bcl-x expression which are respectively regulated by the PI 3-kinase/Akt pathway and STAT5 probably explain this cooperation. Furthermore, we showed by co-immunoprecipitation studies and pull down experiments with fusion proteins encoding the GST-SH2 domains of p85 that STAT5 in its phosphorylated form interacts with the p85 subunit of the PI 3-kinase. These results indicate that the activations of STAT5 and the PI 3-kinase by IL-3 in Ba/F3 cells are tightly connected and cooperate to mediate IL-3-dependent suppression of apoptosis by modulating Bad phosphorylation and Bcl-x expression.

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Section: Introductionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cooperation between STAT5 and phosphatidylinositol 3-kinase in the IL-3-dependent survival of a bone marrow derived cell line

et al. 2000

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“…The expression or function of each member of this superfamily is known to be regulated in response to specific death triggers. For example, in hematopoietic cells, an antiapoptotic member, Bcl-x L , is downregulated by cytokine withdrawal through inactivation of JAK-STAT pathways, [6][7][8][9][10] while DNA damage induced by ionizing radiation (IR) usually does not alter its expression levels. 11 In contrast, IR induces a proapoptotic member, Bax, by activating p53-dependent pathways, 12 while cytokine withdrawal does not.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of thymidine kinase-mediated killing of malignant glioma by BimS, a BH3-only cell death activator

et al. 2003

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Erythropoietin and Erythropoietin Receptor: History, Structure, Interactions, and Intracellular Signal Transduction

Ghaffari

Constantinescu

2004

Wiley Encyclopedia of Molecular Medicine

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Erythropoietin (Epo) is essential for formation of red blood cells. Recombinant Epo has been improving life of thousands of patients with anemia such as renal patients around the world. More recently, it has become clear that Epo may also regulate the behavior of other cell types such as neuronal cells, where Epo exerts an antiapoptotic effect. Understanding the modality of action of Epo in erythroid cells will help in characterizing the role of Epo in other cell types where Epo‐receptor (EpoR) is expressed.

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IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

Cited by 146 publications

References 68 publications

Cooperation between STAT5 and phosphatidylinositol 3-kinase in the IL-3-dependent survival of a bone marrow derived cell line

Cooperation between STAT5 and phosphatidylinositol 3-kinase in the IL-3-dependent survival of a bone marrow derived cell line

Enhancement of thymidine kinase-mediated killing of malignant glioma by BimS, a BH3-only cell death activator

Erythropoietin and Erythropoietin Receptor: History, Structure, Interactions, and Intracellular Signal Transduction

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