MKP3 mediates the cellular response to FGF8 signalling in the vertebrate limb
Author: ["Yasuhiko Kawakami","Joaquín Rodríguez-León","Christopher M. Koth","Dirk Büscher","Tohru Itoh","Ángel Raya","Jennifer K. Ng","Concepción Rodríguez Esteban","Shigeru Takahashi","Domingos Henrique","May-Fun Schwarz","Hiroshi Asahara","Juan Carlos Izpisúa Belmonte"]
Publication: Nature Cell Biology
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Abstract
The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol-3-OH kinase (PI(3)K)/Akt pathways are involved in the regulatory mechanisms of several cellular processes including proliferation, differentiation and apoptosis. Here we show that during chick, mouse and zebrafish limb/fin development, a known MAPK/ERK regulator, Mkp3, is induced in the mesenchyme by fibroblast growth factor 8 (FGF8) signalling, through the PI(3)K/Akt pathway. This correlates with a high level of phosphorylated ERK in the apical ectodermal ridge (AER), where Mkp3 expression is excluded. Conversely, phosphorylated Akt is detected only in the mesenchyme. Constitutively active Mek1, as well as the downregulation of Mkp3 by small interfering RNA (siRNA), induced apoptosis in the mesenchyme. This suggests that MKP3 has a key role in mediating the proliferative, anti-apoptotic signalling of AER-derived FGF8.
Cite this article
Kawakami, Y., Rodríguez-León, J., Koth, C. et al. MKP3 mediates the cellular response to FGF8 signalling in the vertebrate limb. Nat Cell Biol 5, 513–519 (2003). https://doi.org/10.1038/ncb989
