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

doi:10.1016/j.bbrc.2012.04.049

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

Producción científica: Article › revisión exhaustiva

22 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	651-657
Número de páginas	7
Publicación	Biochemical and Biophysical Research Communications
Volumen	421
N.º	4
DOI	https://doi.org/10.1016/j.bbrc.2012.04.049
Estado	Published - may 18 2012

Nota bibliográfica

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 ).

Financiación

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 ).

Financiadores	Número del financiador
973 Project of Ministry of Science and Technology of China	2011CB910502
National Key Research Project	2012AA021703
Tsinghua Internal Research Funds	2011Z01011, 2011THZ02-20
National Natural Science Foundation of China (NSFC)	31071225

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2012.04.049

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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.",

keywords = "Degradation, EGFR, Internalization, MAPK signaling, Rab21",

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

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 ).",

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AU - Yang, Xi

AU - Zhang, Yanquan

AU - Li, Shan

AU - Liu, Chunxiao

AU - Jin, Zhe

AU - Wang, Yinyin

AU - Ren, Fangli

AU - Chang, Zhijie

N1 - 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 ).

PY - 2012/5/18

Y1 - 2012/5/18

N2 - 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.

AB - 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.

KW - Degradation

KW - EGFR

KW - Internalization

KW - MAPK signaling

KW - Rab21

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

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Nota bibliográfica

Financiación

ASJC Scopus subject areas

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