title: Rab21 attenuates EGF-mediated MAPK signaling through enhancing EGFR internalization and degradation.
abstract: Epidermal growth factor (EGF) receptor (EGFR) signal transduction is regulated by endocytosis where many Rab proteins play an important role in the determination of the receptor recycle or degradation. In an effort to better understand how EGF signaling is regulated, we examined the role of Rab21 in regulation of the degradation and signal transduction of the EGFR. Using a transient expression protocol in HEK293T and HeLa cells, we found that Rab21 enhanced the degradation of EGFR through accelerating its internalization in both EGF-independent and EGF-dependent manners. We further demonstrated that Rab21 interacted with EGFR by immunoprecipitation experiments. Interestingly, we observed that overexpression of Rab21 attenuated EGF-mediated mitogen-activated protein kinase (MAPK) signaling by inducing EGFR degradation. Taken together, these data suggest that Rab21 plays a negative role in the EGF-mediated MAPK signaling pathway.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, National Engineering Laboratory for Anti-Tumor Therapeutics, Tsinghua University, Beijing 100084, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Yanquan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Wang
authors.forename: Fangli
authors.initials: F
authors.lastname: Ren
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
mesh_terms: D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D059748:Proteolysis; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D020929:Mitogen-Activated Protein Kinase Kinases; C415145:RAB21 protein, human; D020691:rab GTP-Binding Proteins