p38 MAPK-regulated EGFR internalization takes place in keratinocyte monolayer during stress conditions

The epidermis is the outermost protection of the organism. As so, defence program has to be initiated in stress situation in order to protect keratinocytes. The EGF receptor (EGFR) controls cell proliferation and migration in keratinocytes, being a major regulator of keratinocyte homeostasis within the epidermis. The EGFR is known to be internalized without addition of ligand under the control of p38 MAPK during stress conditions in HeLa cells, but also following lipid rafts disruption in keratinocytes. This could represent an alternative internalization process that removes the EGFR from cell surface. Here, we investigated whether other stress conditions such as scratch wounding keratinocyte monolayer or incubation with a sensitizer chemical (i.e. DNFB), could also induce this peculiar mechanism of EGFR internalization. Our results show that both stressing conditions induce p38 MAPK activation concomitantly with EGFR internalization, independently of ligand binding to the EGFR. Inhibition of p38 MAPK activity during scratch wound blocks EGFR internalization at the margin of the wound while cell migration is impeded. Our results show thus that the p38 MAPK-dependent EGFR internalization is a process shared by keratinocytes when submitted to challenging conditions.