The Stability of the Lens-specific Maf Protein is Regulated by Fibroblast Growth Factor (FGF)/ERK Signaling in Lens Fiber Differentiation*
The Stability of the Lens-specific Maf Protein is Regulated by Fibroblast Growth Factor (FGF)/ERK Signaling in Lens Fiber Differentiation*
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DOI：
10.1074/jbc.m208380200
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发表时间：
2003-01
期刊：
影响因子：
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通讯作者：
H. Ochi;H. Ogino;Y. Kageyama;K. Yasuda
中科院分区：
文献类型：
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作者：
H. Ochi;H. Ogino;Y. Kageyama;K. Yasuda
成纤维细胞生长因子(成纤维细胞生长因子)信号对晶状体细胞的增殖和分化是必需的。然而，FGFs作用于晶状体的分子机制仍然知之甚少。在这项研究中，我们发现在原代培养的晶状体细胞中，成纤维细胞生长因子-2抑制了晶状体特异基因的表达。利用转基因细胞，我们还发现晶状体分化因子L-MAF的活性受到成纤维细胞生长因子/ERK信号的抑制。L-MAF被ERK磷酸化，并且在L-MAF上的ERK靶点引入突变促进了它的稳定。稳定的L-MAF突变蛋白促进晶状体细胞向神经视网膜细胞分化。综上所述，这些结果表明，在增殖的晶状体细胞中，成纤维细胞生长因子/ERK信号负性调节L-MAF的功能，L-MAF蛋白的稳定对晶状体纤维的分化具有重要意义。
Fibroblast growth factor (FGF) signaling is necessary for both proliferation and differentiation of lens cells. However, the molecular mechanisms by which FGFs exert their effects on the lens remain poorly understood. In this study, we show that FGF-2 repressed the expression of lens-specific genes at the proliferative phase in primary cultured lens cells. Using transfected cells, we also found that the activity of L-Maf, a lens differentiation factor, is repressed by FGF/ERK signaling. L-Maf is shown to be phosphorylated by ERK, and introduction of mutations into the ERK target sites on L-Maf promotes its stabilization. The stable L-Maf mutant protein promotes the differentiation of lens cells from neural retina cells. Taken together, these results indicate that FGF/ERK signaling negatively regulates the function of L-Maf in proliferative lens cells and that stabilization of the L-Maf protein is important for lens fiber differentiation.