Reference : The oncogenic FIP1L1-PDGFRalpha fusion protein displays skewed signaling properties c...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/22328
The oncogenic FIP1L1-PDGFRalpha fusion protein displays skewed signaling properties compared to its wild-type PDGFRalpha counterpart.
English
Haan, Serge mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Bahlawane, Christelle mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Wang, Jiali mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Nazarov, Petr V. [> >]
Muller, Arnaud [> >]
Eulenfeld, Rene [> >]
Haan, Claude 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]
Vallar, Laurent [> >]
Satagopam, Venkata mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Sauter, Thomas mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Wiesinger, Monique mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
2015
JAK-STAT
4
1
e1062596
Yes (verified by ORBilu)
International
2162-3988
United States
[en] AKT ; FIP1L1-PDGFRalpha ; Janus kinase ; MAP kinase ; Platelet-derived growth factor ; SH2-domain ; STAT-factor ; Src kinase
[en] Aberrant activation of oncogenic kinases is frequently observed in human cancers, but the underlying mechanism and resulting effects on global signaling are incompletely understood. Here, we demonstrate that the oncogenic FIP1L1-PDGFRalpha kinase exhibits a significantly different signaling pattern compared to its PDGFRalpha wild type counterpart. Interestingly, the activation of primarily membrane-based signal transduction processes (such as PI3-kinase- and MAP-kinase- pathways) is remarkably shifted toward a prominent activation of STAT factors. This diverging signaling pattern compared to classical PDGF-receptor signaling is partially coupled to the aberrant cytoplasmic localization of the oncogene, since membrane targeting of FIP1L1-PDGFRalpha restores activation of MAPK- and PI3K-pathways. In stark contrast to the classical cytokine-induced STAT activation process, STAT activation by FIP1L1-PDGFRalpha does neither require Janus kinase activity nor Src kinase activity. Furthermore, we investigated the mechanism of STAT5 activation via FIP1L1-PDGFRalpha in more detail and found that STAT5 activation does not involve an SH2-domain-mediated binding mechanism. We thus demonstrate that STAT5 activation occurs via a non-canonical activation mechanism in which STAT5 may be subject to a direct phosphorylation by FIP1L1-PDGFRalpha.
University of Luxembourg - UL
http://hdl.handle.net/10993/22328
10.1080/21623996.2015.1062596
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