Open Close
Reference
Citation
Auer, J.S., Nagel, A.C., Schulz, A., Wahl, V., Preiss, A. (2015). MAPK-dependent phosphorylation modulates the activity of Suppressor of Hairless in Drosophila.  Cell. Signal. 27(1): 115--124.
FlyBase ID
FBrf0227416
Publication Type
Research paper
Abstract

Cell differentiation strictly depends on the epidermal growth factor receptor (EGFR)- and Notch-signalling pathways, which are closely intertwined. Here we address the molecular cross talk at the level of Suppressor of Hairless Su(H). The Drosophila transcription factor Su(H) mediates Notch signalling at the DNA level: in the presence of signalling input Su(H) assembles an activator complex on Notch target genes and a repressor complex in its absence. Su(H) contains a highly conserved mitogen activated protein kinase (MAPK) target sequence. Here we provide evidence that Su(H) is phosphorylated in response to MAPK activity. Mutation of the Su(H) MAPK-site modulated the Notch signalling output: whereas a phospho-deficient Su(H)(MAPK-ko) isoform provoked a stronger Notch signalling activity, a phospho-mimetic Su(H)(MAPK-ac) mutant resulted in its attenuation. In vivo assays in Drosophila cell culture as well as in flies support the idea that Su(H) phosphorylation affects the dynamics of repressor or activator complex formation or the transition from the one into the other complex. In summary, the phosphorylation of Su(H) attenuates Notch signalling in vivo in several developmental settings. Consequently, a decrease of EGFR signal causes an increase of Notch signalling intensity. Hence, the antagonistic relationship between EGFR- and Notch-signalling pathways may involve a direct modification of Su(H) by MAPK in several developmental contexts of fly development. The high sequence conservation of the MAPK target site in the mammalian Su(H) homologues supports the idea that EGFR signalling impacts on Notch activity in a similar way in humans as well.

PubMed ID
PubMed Central ID
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell. Signal.
    Title
    Cellular Signalling
    Publication Year
    1988-
    ISBN/ISSN
    0898-6568
    Data From Reference
    Genes (8)
    Physical Interactions (3)
    Cell Lines (1)