Article (Scientific journals)
JAK2-V617F-induced MAPK activity is regulated by PI3K and acts synergistically with PI3K on the proliferation of JAK2-V617F-positive cells.
Wolf, Alexandra; Eulenfeld, Rene; Gäbler, Karoline et al.
2013In JAK-STAT, 2 (3), p. 24574
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Keywords :
Gab1; JAK; JAK2-V617F; MAPK; PI3K; STAT; essential thrombocythemia; myeloid disorders; polycythemia vera; signal transduction
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Wolf, Alexandra
Eulenfeld, Rene
Gäbler, Karoline ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Rolvering, Catherine ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Haan, Serge ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Behrmann, Iris ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Denecke, Bernd
Haan, Claude ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Schaper, Fred
Language :
English
Title :
JAK2-V617F-induced MAPK activity is regulated by PI3K and acts synergistically with PI3K on the proliferation of JAK2-V617F-positive cells.
Publication date :
2013
Journal title :
JAK-STAT
ISSN :
2162-3988
Volume :
2
Issue :
3
Pages :
e24574
Peer reviewed :
Peer reviewed
Commentary :
FULL TEXT available under: https://www.landesbioscience.com/journals/jak-stat/article/24574/
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since 10 January 2014

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