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-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.
Smith
Terence Gordon
TG
Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK. tel_smith@yahoo.co.uk
Karlsson
Maria
M
Lunn
J Simon
JS
Eblaghie
Maxwell C
MC
Keenan
Iain D
ID
Farrell
Elizabeth R
ER
Tickle
Cheryll
C
Storey
Kate G
KG
Keyse
Stephen M
SM
D000818:Animals; D002642:Chick Embryo; D054642:Dual Specificity Phosphatase 6; D004815:Epidermal Growth Factor / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis*; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis*
D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D010749:Phosphoprotein Phosphatases; D054642:Dual Specificity Phosphatase 6; C517036:Dusp6 protein, mouse; D017027:Protein Tyrosine Phosphatases