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Negative feedback predominates over cross‐regulation to control ERK MAPK activity in response to FGF signalling in embryos
Author(s) -
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.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.06.081
Subject(s) - mapk/erk pathway , microbiology and biotechnology , phosphatase , intracellular , protein phosphatase 2 , fibroblast growth factor , signalling , embryonic stem cell , signal transduction , biology , chemistry , phosphorylation , gene , biochemistry , receptor
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.