MKP3 mediates the cellular response to FGF8 signalling in the vertebrate limb
MKP3 mediates the cellular response to FGF8 signalling in the vertebrate limb
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DOI：
10.1038/ncb989
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发表时间：
2003-06-01
影响因子：
21.3
通讯作者：
Belmonte, JCI
中科院分区：
文献类型：
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作者：
Kawakami, Y;Rodríguez-León, J;Belmonte, JCI
丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）和磷脂酰肌醇-3-OH激酶（PI（3）K）/Akt信号通路参与细胞增殖、分化和凋亡等过程的调控。在这里，我们表明，在鸡，小鼠和斑马鱼肢/鳍发育，一个已知的MAPK/ERK调节，Mkp3，诱导间充质中的成纤维细胞生长因子8（FGF8）信号，通过PI（3）K/Akt途径。这与顶端外胚层嵴（AER）中高水平的磷酸化ERK相关，其中Mkp3表达被排除在外。相反，磷酸化Akt仅在间充质中检测到。组成型活性Mek1，以及下调Mkp3的小干扰RNA（siRNA），诱导间充质细胞凋亡。这表明MKP 3在介导AER衍生的FGF 8的增殖、抗凋亡信号传导中具有关键作用。
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.