MKP3 mediates the cellular response to FGF8 signalling in the vertebrate limb

被引：221
作者：
Kawakami, Y
Rodríguez-León, J
Koth, CM
Büscher, D
Itoh, T
Raya, A
Ng, JK
Esteban, CR
Takahashi, S
Henrique, D
Schwarz, MF
Asahara, H
Belmonte, JCI
机构：
[1] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
[2] Gulbenkian Inst Sci, P-2780901 Oeiras, Portugal
[3] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA
[4] Fac Med Lisbon, Inst Histol & Embriol, P-1649028 Lisbon, Portugal
[5] Japan Sci & Technol Corp, PRESTO, Kawaguchi, Saitama 3320012, Japan
来源：
NATURE CELL BIOLOGY | 2003年 / 5卷 / 06期
基金：
加拿大健康研究院; 美国国家卫生研究院; 日本学术振兴会;
关键词：
D O I：
10.1038/ncb989
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
引用
收藏
页码：513 / 519
页数：7
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