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

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-31Pyst1 expression is sensitive to inhibition of ERK or MAPKK, that endogenous MKP-31Pyst1 co-localizes with activated ERK, and expression of MKP-31Pyst1 in mice lacking PDK1, an essential mediator of PI(3)K signalling. We conclude that MKP-31Pyst1 expression is mediated by ERK activation and that negative feedback control predominates in limiting the extent of FGF-induced ERK activity. (c) 2006 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.