title: The Soluble Heparin-Binding EGF-Like Growth Factor Stimulates EGF Receptor Trafficking to the Nucleus.
abstract: Most ligands of epidermal growth factor receptor (EGFR) have the ability to induce EGFR translocation into the nucleus, where EGFR acts as an important transcriptional regulator. Soluble form of heparin-binding EGF-like growth factor (sHB-EGF) is one of the ligands for EGFR in many cell types; however, there is no evidence for the ability of sHB-EGF to induce EGFR nuclear importation. Here, we demonstrated that treatment of A431 cells with sHB-EGF resulted in nuclear localization of EGFR and such translocation occurs via retrograde pathway. It was shown by confocal microscopy and co-immunoprecipitation assay that the translocation complex consisted of both ligand and receptor. The chromatin immunoprecipitation assay showed the association of sHB-EGF-EGFR complex with promoter region of cyclin D1 in the cell nucleus and this association was prevented by application of EGFR kinase inhibitor AG-1478. The obtained data suggest that sHB-EGF acts similarly to other EGFR ligands and is capable to induce EGFR nuclear translocation as a part of ligand-receptor complex in a tyrosine phosphorylation-dependent manner.
authors.affiliation: Molecular Immunology Department, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Nataliia V
authors.initials: NV
authors.lastname: Korotkevych
authors.affiliation: Molecular Immunology Department, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Andrii Ju
authors.initials: AJ
authors.lastname: Labyntsev
authors.affiliation: Molecular Immunology Department, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Denis V
authors.initials: DV
authors.lastname: Kolybo
authors.affiliation: Molecular Immunology Department, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Serhiy V
authors.initials: SV
authors.lastname: Komisarenko
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D066257:Heparin-binding EGF-like Growth Factor; D008024:Ligands; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D020032:Tyrphostins; D019938:Cyclin D1; C101044:RTKI cpd; C512478:EGFR protein, human; D066246:ErbB Receptors