title: Spatiotemporally-regulated interaction between β1 integrin and ErbB4 that is involved in fibronectin-dependent cell migration.
abstract: Integrins are widely expressed cell surface molecules that mediate cell attachment to extracellular matrix (ECM) proteins. They also interact with molecules on their own membranes, and these cis-interactions play a crucial role in integrin-dependent cellular responses. We herein analysed what molecules interact with β1 integrin during biological events induced by cell attachment to different ECM proteins, using a recently established reaction, the enzyme-mediated activation of radical sources (EMARS). The interactions between β1 integrin and receptor tyrosine kinases including EGFR and ErbB4 reached a peak at 2 h after seeding HeLa S3 cells onto the ECM proteins. The peak of phosphorylation of ErbB4 (at 2 h after seeding the cells onto fibronectin) coincided with the peak of the interaction with β1 integrin, while that of EGFR (at 1 day) did not. Accompanying with these findings, suppression of cell migration by a pharmacological inhibitor of the ErbB family receptors, PD168393 and an anti-ErbB4 neutralizing antibody, 12D8 was observed at 2 h after seeding. Taken together, it is deduced that interactions between β1 integrin and ErbB4 occur in a spatiotemporally-regulated manner, and such interaction contributes to the integrin-dependent cell migration.
authors.affiliation: Department of Biochemistry, Kochi System Glycobiology Center, Kochi University Medical School, Nankoku, Kochi, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Yamashita
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kotani
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ishiura
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Honke
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D066247:Receptor, ErbB-4
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4