Spatio-temporal regulation of EGFR signaling by the Eps15 homology domain-containing protein 3 (EHD3).

ABSTRACT: The epidermal growth factor (EGF) receptor EGFR is a major receptor tyrosine kinase whose role in gliomagenesis is well established. We have recently identified EHD3 [Eps15 homology (EH) domain-containing protein 3], an endocytic trafficking regulatory protein, as a putative brain tumor suppressor. Here, we investigate the underlying mechanisms, by establishing a novel mechanistic and functional connection between EHD3 and the EGFR signaling pathway. We show that, in response to stimulation with the EGF ligand, EHD3 accelerates the rate of EGFR degradation by dramatically increasing its ubiquitination. As part of this process, EHD3 also regulates EGFR endosomal trafficking by diverting it away from the recycling route into the degradative pathway. Moreover, we found that upon EGF activatio

SUBMITTER: Amessou M 

PROVIDER: S-EPMC5346708 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature