Rab21Attenuates EGF-mediated MAPK Signaling Through Enhancing EGFR Internalization And Degradation

Epidermal growth factor (EGF) receptor (EGFR) signal transduction isregulated by endocytosis where many Rab proteins play an important role in thedetermination of the receptor recycle or degradation. In an effort to betterunderstand how EGF signaling is regulated, we examined the role of Rab21inregulation of the degradation and signal transduction of the EGFR. Using atransient expression protocol in HEK293T and HeLa cells, we found that Rab21enhanced the degradation of EGFR through accelerating its internalization inboth EGF-independent and EGF-dependent manners. We further demonstratedthat Rab21interacted with EGFR by immunoprecipitation experiments.Interestingly, we observed that overexpression of Rab21attenuatedEGF-mediated mitogen-activated protein kinase (MAPK) signaling by inducingEGFR degradation. Taken together, these data suggest that Rab21plays anegative role in the EGF-mediated MAPK signaling pathway.