Negative feedback predominates over cross-regulation to control ERK MAPK activity in response to FGF signalling in embryos |
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| Authors: | Smith Terence Gordon Karlsson Maria Lunn J Simon Eblaghie Maxwell C Keenan Iain D Farrell Elizabeth R Tickle Cheryll Storey Kate G Keyse Stephen M |
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| Affiliation: | Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK. tel_smith@yahoo.co.uk |
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| 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. |
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| Keywords: | Negative feedback Fibroblast growth factor Extracellular signal-regulated kinase Mitogen activated protein kinase MKP-3/Pyst1 Limb |
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