Knudsen Stine Louise Jeppe, Mac Anni Sieu Wai, Henriksen Lasse, van Deurs Bo, Grøvdal Lene Melsæther
Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen , Denmark .
Growth Factors. 2014 Oct;32(5):155-63. doi: 10.3109/08977194.2014.952410.
EGF receptor (EGFR) and its signaling have been investigated for many years, but how its different ligands regulate signaling has not been thoroughly explored. When investigating EGFR activation and downstream signaling in HeLa cells using a panel of ligands, we found a ligand-dependent differential activation of EGFR and the signaling pathways Akt, PLCγ and STAT with HB-EGF and BTC being the most potent ligands. All the tested ligands induced full activation of Erk signaling at 1 nM, whereas only HB-EGF and partly BTC and EGF induced strong activation of Akt, STAT3 and PLCγ at this concentration. Interestingly, we also found that the high activation potencies of HB-EGF and BTC could only partially be explained by their binding affinities, and are therefore likely to be regulated by other mechanisms. We thus suggest that the signaling pathways initiated from the EGFR vary depending on the ligands bound in a cell specific manner.
表皮生长因子受体（EGFR）及其信号传导已被研究多年，但不同配体如何调节信号传导尚未得到充分探索。当使用一组配体研究HeLa细胞中的EGFR激活和下游信号传导时，我们发现EGFR以及Akt、PLCγ和STAT信号通路存在配体依赖性差异激活，其中肝素结合表皮生长因子（HB-EGF）和双向调节蛋白（BTC）是最有效的配体。所有测试配体在1 nM时均诱导Erk信号的完全激活，而在此浓度下，只有HB-EGF以及部分BTC和表皮生长因子（EGF）诱导Akt、信号转导和转录激活因子3（STAT3）和PLCγ的强烈激活。有趣的是，我们还发现HB-EGF和BTC的高激活效力只能部分地由它们的结合亲和力来解释，因此可能受其他机制调节。因此，我们认为从EGFR起始的信号通路根据细胞特异性结合的配体而有所不同。
