An alternative EGFR activation by patient-derived R252C mutation promotes cancer progression.

ABSTRACT: Mutations in the extracellular or intracellular domains of epidermal growth factor receptor (EGFR) are implicated in the development of various cancers. While the intracellular mutations of EGFR have been extensively studied, the function of extracellular mutations remains poorly understood. In this study, we identify an EGFR mutant (EGFR R252C) in a patient with multifocal lung cancer and glioma, in which arginine (R) 252 is mutated to cysteine (C) in the EGFR extracellular domain. This mutation promotes C252-C252 disulfide-mediated EGFR dimerization and induces a conformational change of EGFR, leading to absent autophosphorylation and enhanced direct interaction between EGFR and extracellular signal-regulated protein kinase 1/2 (ERK1/2). Importantly, EGFR directly phosphorylates ERK1/2 a

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12923773 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature