FGF signalling modulates transcriptional repression by Xenopus groucho-related-4
FGF signalling modulates transcriptional repression by Xenopus groucho-related-4
复制标题
DOI：
10.1042/bc20080136
复制
发表时间：
2009-05-01
影响因子：
2.7
通讯作者：
Pownall, Mary E.
中科院分区：
文献类型：
--
作者：
Burks, Patrick J.;Isaacs, Harry V.;Pownall, Mary E.
背景资料。在胚胎发生过程中，发育细胞信号在细胞特化和组织形成过程中相互配合。FGF（成纤维细胞生长因子）和Wnt信号通路之间的相互作用已经在许多发育过程中得到证实，包括两栖动物胚胎中的中胚层形成。然而，这些关键信号通路之间的相互作用的机制仍然不清楚。在本研究中，我们发现TLE 4/Xgrg 4（transformin-like enhancer of split 4/Xenopus groucho-related gene 4）抑制经典Writ信号转导靶点的能力在FGF存在下降低，这部分依赖于TLE 4/Xgrg 4中MAPK（mitogen-activated protein kinase）磷酸化的共有位点。这些数据向我们提示了一种新的分子机制，其中FGF和Wnt信号传导途径在共阻遏物TLE 4/Xgrg 4水平上相互作用：FGF信号传导对TLE 4/Xgrg 4阻遏的减弱，结合Wnt信号对β-连环蛋白的稳定，增强了Wnt靶基因的表达。
Background information. Developmental cell signals co-operate in the processes of cell specification and tissue patterning during embryogenesis. Interactions between the FGF (fibroblast growth factor) and Wnt signalling pathways have been demonstrated in a number of developmental processes, including mesoderm formation in amphibian embryos. However, the mechanism underlying the interactions between these key signalling pathways remains unclear.Results. In the present study, we find that the ability of TLE4/Xgrg4 (transducin-like enhancer of split 4/Xenopus groucho-related gene 4) to inhibit a transcriptional target of canonical Writ signalling is reduced in the presence of FGF and that this is partially dependent on a consensus site for MAPK (mitogen-activated protein kinase) phosphorylation in TLE4/Xgrg4.Conclusions. These data suggest to us a novel molecular mechanism where FGF and Wnt signalling pathways interact at the level of the co-repressor TLE4/Xgrg4: the weakening of TLE4/Xgrg4 repression by FGF signalling, combined with the stabilization of beta-catenin by Wnt signals, enhances expression of Wnt target genes.