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    Scaffolding by ERK3 Regulates MK5 in Development (2004)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Schumacher, Stefanie
    Laass, Kathrin
    Kant, Shashi
    Shi, Yu
    Visel, Axel
    Gruber, Achim D (WE 12)
    Kotlyarov, Alexey
    Gaestel, Matthias
    Quelle
    The EMBO journal; 23(24) — S. 4770–4779
    ISSN: 0261-4189
    Sprache
    Englisch
    Verweise
    Pubmed: 15538386
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    +49 30 838 62450

    Abstract / Zusammenfassung

    Extracellular-regulated kinase 3 (ERK3, MAPK6) is an atypical member of the ERKs, lacking the threonine and tyrosine residues in the activation loop, carrying a unique C-terminal extension and being mainly regulated by its own protein stability and/or by autophosphorylation. Here we show that ERK3 specifically interacts with the MAPK-activated protein kinase 5 (MK5 or PRAK) in vitro and in vivo. Expression of ERK3 in mammalian cells leads to nuclear-cytoplasmic translocation and activation of MK5 and to phosphorylation of both ERK3 and MK5. Remarkably, activation of MK5 is independent of ERK3 enzymatic activity, but depends on its own catalytic activity as well as on a region in the C-terminal extension of ERK3. In mouse embryonic development, mRNA expression patterns of ERK3 and MK5 suggest spatiotemporal coexpression of both kinases. Deletion of MK5 leads to strong reduction of ERK3 protein levels and embryonic lethality at about stage E11, where ERK3 expression in wild-type mice is maximum, indicating a role of this signalling module in development.