P38 MAP kinase mediates stress-induced internalization of EGFR: implications for cancer chemotherapy.

ABSTRACT: The epidermal growth factor receptor (EGFR) frequently associates with cancer and already serves as a target for therapy. We report that inflammatory cytokines and ultraviolet (UV) irradiation respectively induce transient or sustained phosphorylation of EGFR. Subsequently, EGFR internalizes via a Clathrin-mediated process. In cytokine-stimulated cells, EGFR recycles back to the cell surface, whereas in irradiated cells it arrests in Rab5-containing endosomes. Under both conditions, receptor internalization is instigated by the p38 stress-induced kinase. The underlying mechanism entails phosphorylation of EGFR at a short segment (amino acids 1002-1022) containing multiple serines and threonines, as well as phosphorylation of two Rab5 effectors, EEA1 and GDI. Like UV irradiation, a chemothe

SUBMITTER: Zwang Y 

PROVIDER: S-EPMC1570432 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature