Abstract 264: EGFR endocytosis after binding of different ligands

Abstract

Abstract The EGF receptor (EGFR) is activated by binding of ligand, leading to both signaling and receptor endocytosis. This endocytosis can lead to receptor downregulation, or recycling. Although EGFR regulation has received much attention, most studies have been performed using either EGF or TGFα. We described EGFR endocytosis upon binding of four additional ligands. Even though all ligands induce internalization, degradation of the receptor is dependent on the nature of the ligand bound. We have shown that the different ligands vary in levels of EGFR activation, receptor ubiquitination, and also in pH-stability of receptor-ligand interaction. We found that whereas HB-EGF and betacellulin are strong inducers of EGFR degradation, TGFα and epiregulin mostly allow for recycling of the EGFR. Amphiregulin also allows for recycling of the EGFR, but by a slower pathway. EGF leads to both recycling and degradation of the EGFR. We now show that, in addition to intracellular sorting in endosomes, the mechanism of internalization of the EGFR from the plasma membrane also differs depending on which ligand is bound. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 264.