c-Cbl-mediated ubiquitinylation is required for epidermal growth factor receptor exit from the early endosomes.

摘要: Epidermal growth factor receptor (EGFR) controls cell and has a key role in tumorigenic processes. The extent of EGFR signaling is tightly regulated by post-transcriptional modifications leading to down-regulation the levels receptor. Previous studies from our laboratory demonstrated that reactive oxidant hydrogen peroxide activates EGFR, yet, without levels, which results prolonged signaling. In present study we examined E3 ligase c-Cbl, as possible link between oxidative stress, signaling, responses. First, ectopically expressed mutant (Tyr-1045 → Phe) cells lacking endogenous receptor, determine whether lack phosphorylation at this site cause for retention membrane under have previously suggested. Our findings suggest abrogation tyrosine 1045 alone not enough retain plasma stress. Second, through use Src inhibitor PP1, establish movement out early endosomes exact location where c-Cbl-mediated ubiquitinylation essential trafficking. Finally, substantiate needed degradation, but internalization both transfection-dependent Chinese hamster ovary transfection-independent A549 lung epithelial cells. These only begin explain features seen they yield greater understanding c-Cbl