Negative feedback predominates over cross-regulation to control ERK MAPK activity in response to FGF signalling in embryos

Terence Gordon Smith, Maria Karlsson, J Simon Lunn, Maxwell C Eblaghie, Iain D Keenan, Elizabeth R Farrell, Cheryll Tickle, Kate G Storey, Stephen M Keyse

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    41 Citations (Scopus)

    Abstract

    Expression of the gene encoding the MKP-3/Pyst1 protein phosphatase, which inactivates ERK MAPK, is induced by FGF. However, which intracellular signalling pathway mediates this expression is unclear, with essential roles proposed for both ERK and PI(3)K in chick embryonic limb. Here, we report that MKP-3/Pyst1 expression is sensitive to inhibition of ERK or MAPKK, that endogenous MKP-3/Pyst1 co-localizes with activated ERK, and expression of MKP-3/Pyst1 in mice lacking PDK1, an essential mediator of PI(3)K signalling. We conclude that MKP-3/Pyst1 expression is mediated by ERK activation and that negative feedback control predominates in limiting the extent of FGF-induced ERK activity.
    Original languageEnglish
    Pages (from-to)4242-5
    Number of pages4
    JournalFEBS Letters
    Volume580
    Issue number17
    DOIs
    Publication statusPublished - 2006

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