Article (Scientific journals)
The oncogenic FIP1L1-PDGFRalpha fusion protein displays skewed signaling properties compared to its wild-type PDGFRalpha counterpart.
Haan, Serge; Bahlawane, Christelle; Wang, Jiali et al.
2015In JAK-STAT, 4 (1), p. 1062596
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Keywords :
AKT; FIP1L1-PDGFRalpha; Janus kinase; MAP kinase; Platelet-derived growth factor; SH2-domain; STAT-factor; Src kinase
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Haan, Serge ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Bahlawane, Christelle ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Wang, Jiali ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Nazarov, Petr V.
Muller, Arnaud
Eulenfeld, Rene
Haan, Claude ;  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
Vallar, Laurent
Satagopam, Venkata ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Sauter, Thomas ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Wiesinger, Monique ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
no
Language :
English
Title :
The oncogenic FIP1L1-PDGFRalpha fusion protein displays skewed signaling properties compared to its wild-type PDGFRalpha counterpart.
Publication date :
2015
Journal title :
JAK-STAT
ISSN :
2162-3988
Volume :
4
Issue :
1
Pages :
e1062596
Peer reviewed :
Peer reviewed
Name of the research project :
R-AGR-0085 - IRP11 - PDGFR-KIT (20110101-20141231) - HAAN Serge
Funders :
University of Luxembourg - UL
Available on ORBilu :
since 01 November 2015

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