Spatial recruitment and activation of the Fes kinase by ezrin promotes HGF-induced cell scattering.
EMBO J
; 27(1): 38-50, 2008 Jan 09.
Article
en En
| MEDLINE
| ID: mdl-18046454
ABSTRACT
The remodeling of epithelial monolayers induced by hepatocyte growth factor (HGF) results in the reorganization of actin cytoskeleton and cellular junctions. We previously showed that the membrane-cytoskeleton linker ezrin plays a major role in HGF-induced morphogenic effects. Here we identified a novel partner of phosphorylated ezrin, the Fes kinase, that acts downstream of ezrin in HGF-mediated cell scattering. We found that Fes interacts directly, through its SH2 domain, with ezrin phosphorylated at tyrosine 477. We show that in epithelial cells, activated Fes localizes either to focal adhesions or cell-cell contacts depending on cell confluency. The recruitment and the activation of Fes to the cell-cell contacts in confluent cells depend on its interaction with ezrin. When this interaction is impaired, Fes remains in focal adhesions and as a consequence the cells show defective spreading and scattering in response to HGF stimulation. Altogether, these results provide a novel mechanism whereby ezrin/Fes interaction at cell-cell contacts plays an essential role in HGF-induced cell scattering and implicates Fes in the cross-talk between cell-cell and cell-matrix adhesion.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Movimiento Celular
/
Factor de Crecimiento de Hepatocito
/
Proteínas del Citoesqueleto
/
Proteínas Proto-Oncogénicas c-fes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
EMBO J
Año:
2008
Tipo del documento:
Article
País de afiliación:
Francia