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Constitutively active STAT5 variants induce growth and survival of hematopoietic cells through a PI 3-kinase/Akt dependent pathway

Abstract : Signal Transducer and Activator of Transcription (STATs) are important mediators of cytokine and growth factor-induced signal transduction. STAT5A and STAT5B have been shown to play a role in survival and proliferation of hematopoietic cells both in vitro and in vivo and to contribute to the growth and viability of cells transformed by the TEL-JAK2 oncoprotein. In this study, we investigated the molecular mechanisms by which constitutively active STAT5 proteins induce cell proliferation and survival of Ba/F3 cell lines expressing either dominant positive STAT5A or STAT5B variants or TEL-JAK2 or TEL-ABL fusion proteins. Our results showed that active STAT5 constitutively interacted with p85, the regulatory subunit of the PI 3-kinase. A constitutive activity of the PI 3-kinase/Akt pathway was observed in these cells and required for their cell cycle progression. In contrast, while activity of the PI 3-kinase/Akt pathway was required for survival of Ba/F3 cells expressing the constitutively active forms of STAT5A or STAT5B, it was dispensable for cells transformed by TEL-JAK2 or TEL-ABL fusion proteins, suggesting that additional survival pathways take place in these transformed cells.
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https://hal-univ-tours.archives-ouvertes.fr/hal-02427359
Contributor : Fabrice Gouilleux <>
Submitted on : Friday, January 3, 2020 - 3:13:31 PM
Last modification on : Friday, March 27, 2020 - 2:46:04 AM

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Susana Constantino Rosa Santos, Virginie Lacronique, Isabelle Bouchaert, Richard Monni, Olivier Bernard, et al.. Constitutively active STAT5 variants induce growth and survival of hematopoietic cells through a PI 3-kinase/Akt dependent pathway. Oncogene, Nature Publishing Group, 2001, 20 (17), pp.2080-2090. ⟨10.1038/sj.onc.1204308⟩. ⟨hal-02427359⟩

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