Faria Jerusa A Q A, de Andrade Carolina, Goes Alfredo M, Rodrigues Michele A, Gomes Dawidson A
Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil.
Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil; Department of General Pathology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil.
Biochem Biophys Res Commun. 2016 Sep 9;478(1):39-45. doi: 10.1016/j.bbrc.2016.07.097. Epub 2016 Jul 25.
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.
表皮生长因子受体（EGFR）通过与特定配体结合而被激活，并产生促进增殖、分化、迁移和细胞存活的信号。最近的数据显示了核内EGFR在肿瘤中的作用。尽管许多EGFR配体在癌症中上调，但其对EGFR核转位的影响却知之甚少。我们比较了六种EGFR配体（表皮生长因子（EGF）、肝素结合表皮生长因子（HB-EGF）、转化生长因子-α（TGF-α）、β-细胞ulin、双调蛋白和表皮调节素）对EGFR核转位、受体磷酸化、迁移和增殖的影响。细胞分级分离和共聚焦免疫荧光检测发现，在EGF、HB-EGF、TGF-α和β-细胞ulin刺激后，细胞核中出现剂量依赖性的EGFR。相比之下，双调蛋白和表皮调节素不会引起EGFR的核转位。与双调蛋白和表皮调节素相比，EGF、HB-EGF、TGF-α和β-细胞ulin显示出较高的伤口愈合率与EGFR羧基末端残基磷酸化增加之间的相关性。数据表明，EGF、HB-EGF、TGF-α和β-细胞ulin刺激后EGFR会转位至细胞核，并且这些配体与EGFR酪氨酸残基磷酸化增加有关，可诱导SkHep-1细胞迁移。
