Raf/MAPK and rapamycin-sensitive pathways mediate the anti-apoptotic function of p21Ras in IL-3-dependent hematopoietic cells

Kinoshita, Taisei; Shirouzu, Mikako; Kamiya, Akihide; Hashimoto, Kyoko; Yokoyama, Shigeyuki; Miyajima, Atsushi

doi:10.1038/sj.onc.1201234

Cited by 115 publications

(90 citation statements)

References 51 publications

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“…Con¯icting results regarding the role of MEK/ MAPK in preventing apoptosis have emerged these last years (Kinoshita et al, 1995(Kinoshita et al, , 1997Miike et al, 1999;Scheid and Duronio, 1998). Recently, it has been shown that the MEK inhibitor PD98059 did not prevent the IL-3-or GM-CSF-mediated survival of MC/9 cells but reduced Bad phosphorylation (Scheid and Duronio, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Similarly, over-expression of oncogenic Raf, a downstream target of Ras, also suppressed apoptosis induced by could be overcome by PI3K inhibitors or by the inhibition of p70S6K by rapamycin [131]. Blocking the PI3K/p70S6K IL-3 withdrawal in 32D3 and BaF3 cells [130,131], and inhibition of ERK activation with a dominant-negative MAPKK pathways in other cell types also hints at the involvement of these kinases in survival [145]. Recent advances in the elusuppresses IL-3-dependent survival in BaF3 cells [132].…”

Section: Il-3/il-5/gm-csf Receptor Signallingmentioning

confidence: 98%

Regulation of Proliferation, Differentiation and Survival by the IL-3/IL-5/GM-CSF Receptor Family

Groot

Coffer

Koenderman

1998

Cellular Signalling

191

153

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ABSTRACT. The receptors for the Il-3/IL-5/GM-CSF cytokine family are composed of a heterodimeric complex of a cytokine-specific ␣ chain and a common ␤ chain (␤c). Binding of IL-3/IL-5/GM-CSF to their respective receptors rapidly induces activation of multiple intracellular signalling pathways, including the Ras-Raf-ERK, the JAK/STAT, the phosphatidylinositol 3-kinase PKB, and the JNK/SAPK and p38 signalling pathways. This review focuses on recent advancements in understanding how these different signalling pathways are activated by IL-3/IL-5/GM-CSF receptors, and how the individual pathways contribute to the pleiotropic effects of IL-3/IL-5/GM-CSF on their target cells, including proliferation, differentiation, survival, and effector functions. cell signal 10;9:619-628, 1998.

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“…To identify the signalling pathways responsible for the di erences in the physiological response of BaF Hm and BaF HER cells we examined the activation of PI3-kinase (Figure 2a), the MAP kinase pathway ( Figure 2b) and STAT5 ( Figure 2c) by both the EGFR and the HER-mrk receptor, since it is known that these (Kinoshita et al, 1997;Rosa Santos et al, 2000). Activation of the catalytic activity of PI3-kinase was signi®cantly increased after stimulation of the HERmrk receptor as well as of the EGFR indicated by serine phosphorylation of Akt (Figure 2a), a protein acting further downstream in the PI3-kinase signalling pathway.…”

Section: Her-mrk But Not the Egfr Activates Stat5 In Ba/f3 Cellsmentioning

confidence: 99%

Activation of STAT5 triggers proliferation and contributes to anti-apoptotic signalling mediated by the oncogenic Xmrk kinase

et al. 2002

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Extensive studies of primary tumors and tumor derived cell lines revealed that inappropriate activation of speci®c STATs (particularly of STAT3 and STAT5) occurs with high frequency in a wide variety of human cancers. We reported recently that the melanoma inducing EGFRrelated receptor Xmrk speci®cally induces constitutive activation of STAT5 in ®sh melanoma cells. However, little is known about the role of STAT5 in solid tumours in general and its function in melanoma in particular. Recent examinations suggest that activated STAT signalling participates in oncogenesis by stimulating cell proliferation and preventing apoptosis. As an initial approach to understanding the consequences of Xmrk induced STAT5 signalling we used the well characterized pro B-cell line Ba/F3 as a sensitive system to analyse mitogenic as well as anti-apoptotic signalling. We identi®ed STAT5 activation as being involved in both growth and survival signalling triggered by the Xmrk kinase possibly due to STAT5 induced expression of pim-1 and bcl-x. We also found a new mechanism of activation of STAT5 by receptor tyrosine kinases, whereby direct interaction of the receptor kinase domain with the STAT protein in a phosphotyrosine independent way led to activation of STAT5 in terms of DNA binding and target gene expression.

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Raf/MAPK and rapamycin-sensitive pathways mediate the anti-apoptotic function of p21Ras in IL-3-dependent hematopoietic cells

Cited by 115 publications

References 51 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

Regulation of Proliferation, Differentiation and Survival by the IL-3/IL-5/GM-CSF Receptor Family

Activation of STAT5 triggers proliferation and contributes to anti-apoptotic signalling mediated by the oncogenic Xmrk kinase

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