Reference : JAK2-V617F-induced MAPK activity is regulated by PI3K and acts synergistically with P...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/14741
JAK2-V617F-induced MAPK activity is regulated by PI3K and acts synergistically with PI3K on the proliferation of JAK2-V617F-positive cells.
English
Wolf, Alexandra [> >]
Eulenfeld, Rene [> >]
Gäbler, Karoline mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Rolvering, Catherine mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Haan, Serge mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Denecke, Bernd [> >]
Haan, Claude mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Schaper, Fred [> >]
2013
JAK-STAT
2
3
e24574
Yes (verified by ORBilu)
International
2162-3988
United States
[en] Gab1 ; JAK ; JAK2-V617F ; MAPK ; PI3K ; STAT ; essential thrombocythemia ; myeloid disorders ; polycythemia vera ; signal transduction
[en] The identification of a constitutively active JAK2 mutant, namely JAK2-V617F, was a milestone in the understanding of Philadelphia chromosome-negative myeloproliferative neoplasms. The JAK2-V617F mutation confers cytokine hypersensitivity, constitutive activation of the JAK-STAT pathway, and cytokine-independent growth. In this study we investigated the mechanism of JAK2-V617F-dependent signaling with a special focus on the activation of the MAPK pathway. We observed JAK2-V617F-dependent deregulated activation of the multi-site docking protein Gab1 as indicated by constitutive, PI3K-dependent membrane localization and tyrosine phosphorylation of Gab1. Furthermore, we demonstrate that PI3K signaling regulates MAPK activation in JAK2-V617F-positve cells. This cross-regulation of the MAPK pathway by PI3K affects JAK2-V617F-specific target gene induction, erythroid colony formation, and regulates proliferation of JAK2-V617F-positive patient cells in a synergistically manner.
http://hdl.handle.net/10993/14741
10.4161/jkst.24574
https://www.landesbioscience.com/journals/jak-stat/article/24574/
FULL TEXT available under: https://www.landesbioscience.com/journals/jak-stat/article/24574/

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