Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation.
Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation.
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DOI：
10.1016/j.bbrc.2016.07.097
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发表时间：
2016-09-09
影响因子：
3.1
通讯作者：
Gomes DA
中科院分区：
文献类型：
--
作者：
Faria JAQA;de Andrade C;Goes AM;Rodrigues MA;Gomes DA
表皮生长因子受体（EGFR）通过与特异性配体结合而被激活，并产生增殖、分化、迁移和细胞存活的信号。最近的数据显示了细胞核EGFR在肿瘤中的作用。尽管许多EGFR配体在癌症中上调，但关于它们对EGFR核易位的影响知之甚少。我们比较了6种EGFR配体（EGF、HB-EGF、TGF-α、β-Cellulin、双调蛋白和epiregulin）对EGFR核转位、受体磷酸化、迁移和增殖的影响。EGF、HB-EGF、TGF-α和β-Cellulin刺激后，细胞分级和共聚焦免疫荧光检测到EGFR以剂量依赖的方式存在于细胞核中。相反，双调蛋白和epiregulin不产生EGFR的核转位。EGF、HB-EGF、TGF-α和β-纤维素显示出与双调蛋白和表皮调节蛋白相比，更高的伤口闭合率与EGFR羧基末端残基磷酸化增加之间的相关性。数据表明，在用EGF、HB-EGF、TGF-α和β-纤维素刺激后，EGFR易位至细胞核，并且这些配体与EGFR酪氨酸残基的磷酸化增加有关，从而诱导SkHep-1细胞的迁移。
The epidermal growth factor receptor (EGFR) is activated through binding to specific ligands and generates signals for proliferation, differentiation, migration, and cell survival. Recent data show the role of nuclear EGFR in tumors. Although many EGFR ligands are upregulated in cancers, little is known about their effects on EGFR nuclear translocation. We have compared the effects of six EGFR ligands (EGF, HB-EGF, TGF-α, β-Cellulin, amphiregulin, and epiregulin) on nuclear translocation of EGFR, receptor phosphorylation, migration, and proliferation. Cell fractionation and confocal immunofluorescence detected EGFR in the nucleus after EGF, HB-EGF, TGF-α and β-Cellulin stimulation in a dose-dependent manner. In contrast, amphiregulin and epiregulin did not generate nuclear translocation of EGFR. EGF, HB-EGF, TGF-α and β-Cellulin showed correlations between a higher rate of wound closure and increased phosphorylation of residues in the carboxy-terminus of EGFR, compared to amphiregulin and epiregulin. The data indicate that EGFR is translocated to the nucleus after stimulation with EGF, HB-EGF, TGF-α and β-Cellulin, and that these ligands are related to increased phosphorylation of EGFR tyrosine residues, inducing migration of SkHep-1 cells.