Rab21 attenuates EGF-mediated MAPK signaling through enhancing EGFR internalization and degradation

Xi Yang, Yanquan Zhang, Shan Li, Chunxiao Liu, Zhe Jin, Yinyin Wang, Fangli Ren, Zhijie Chang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)651-657
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume421
Issue number4
DOIs
StatePublished - May 18 2012

Bibliographical note

Funding Information:
We thank Dr. Akihiko Yoshimura (Kyushu University, Fukuoka, Japan) for Elk-1 luciferase reporter plasmids and GFP-Erk2 constructs, and Dr. Arwyn T. Jones (Cardiff University, Cardiff, UK.) for EGFP-Rab21 constructs. This work was supported by grants from 973 Project of China ( 2011CB910502 ), the NSFC ( 31071225 ), National Key Project ( 2012AA021703 ), and the Tsinghua Internal Research Funds ( 2011THZ02-20 , 2011Z01011 ).

Keywords

  • Degradation
  • EGFR
  • Internalization
  • MAPK signaling
  • Rab21

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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