title: EphA2 promotes cell adhesion and spreading of monocyte and monocyte/macrophage cell lines on integrin ligand-coated surfaces.
abstract: Eph signaling, which arises following stimulation by ephrins, is known to induce opposite cell behaviors such as promoting and inhibiting cell adhesion as well as promoting cell-cell adhesion and repulsion by altering the organization of the actin cytoskeleton and influencing the adhesion activities of integrins. However, crosstalk between Eph/ephrin with integrin signaling has not been fully elucidated in leukocytes, including monocytes and their related cells. Using a cell attachment stripe assay, we have shown that, following stimulation with ephrin-A1, kinase-independent EphA2 promoted cell spreading/elongation as well as adhesion to integrin ligand-coated surfaces in cultured U937 (monocyte) and J774.1 (monocyte/macrophage) cells as well as sublines of these cells expressing dominant negative EphA2 that lacks most of the intracellular region. Moreover, a pull-down assay showed that dominant negative EphA2 is recruited to the β2 integrin/ICAM1 and β2 integrin/VCAM1 molecular complexes in the subline cells following stimulation with ephrin-A1-Fc. Notably, this study is the first comprehensive analysis of the effects of EphA2 receptors on integrin-mediated cell adhesion in monocytic cells. Based on these findings we propose that EphA2 promotes cell adhesion by an unknown signaling pathway that largely depends on the extracellular region of EphA2 and the activation of outside-in integrin signaling.
authors.affiliation: a Laboratory of Veterinary Anatomy; Graduate School of Life and Environmental Sciences; Osaka Prefecture University ; Izumisano , Osaka , Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Saeki
authors.affiliation: a Laboratory of Veterinary Anatomy; Graduate School of Life and Environmental Sciences; Osaka Prefecture University ; Izumisano , Osaka , Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nishino
authors.affiliation: a Laboratory of Veterinary Anatomy; Graduate School of Life and Environmental Sciences; Osaka Prefecture University ; Izumisano , Osaka , Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: a Laboratory of Veterinary Anatomy; Graduate School of Life and Environmental Sciences; Osaka Prefecture University ; Izumisano , Osaka , Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D036382:Ephrin-A1 / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008024:Ligands; D009000:Monocytes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D036104:Receptor, EphA2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D036382:Ephrin-A1; C573420:ICAM1 protein, human; D016023:Integrins; D008024:Ligands; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D036104:Receptor, EphA2
keywords: EphA2; ICAM1; U937; cell adhesion; integrins