title: Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation.
abstract: 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.
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil.
authors.forename: Jerusa A Q A
authors.initials: JAQA
authors.lastname: Faria
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: de Andrade
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil.
authors.forename: Alfredo M
authors.initials: AM
authors.lastname: Goes
authors.affiliation: 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.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Rodrigues
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil. Electronic address: dawidson@ufmg.br.
authors.forename: Dawidson A
authors.initials: DA
authors.lastname: Gomes
mesh_terms: D021581:Active Transport, Cell Nucleus; D066259:Betacellulin / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D010766:Phosphorylation; D016211:Transforming Growth Factor alpha / Q000378:metabolism
chemical_list: C587851:BTC protein, human; D066259:Betacellulin; D066257:Heparin-binding EGF-like Growth Factor; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Cell migration; EGFR ligands; Epidermal growth factor receptor; Nuclear translocation; Proliferation; Tyrosine phosphorylation sites