PEA-15 facilitates EGFR dephosphorylation via ERK sequestration at increased ER-PM contacts in TNBC cells

Miyoung Shin; Kyung Eun Lee; Eun Gyeong Yang; Hyesung Jeon; Hyun Kyu Song

doi:10.1016/j.febslet.2015.03.009

PEA-15 facilitates EGFR dephosphorylation via ERK sequestration at increased ER-PM contacts in TNBC cells

Miyoung Shin, Kyung Eun Lee, Eun Gyeong Yang, Hyesung Jeon, Hyun Kyu Song

Division of Life Sciences

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Phosphoprotein enriched in astrocytes of 15kDa (PEA-15) is known to sequester extracellular signal-regulated kinase (ERK) in the cytoplasm, inhibiting tumorigenesis of human breast cancer cells. Here, we describe how PEA-15 expression affects the dephosphorylation of epidermal growth factor receptor (EGFR) through endoplasmic reticulum (ER)-plasma membrane (PM) contacts in MDA-MB-468, triple-negative breast cancer (TNBC) cells. The increased intracellular calcium concentration resulting from increased cytoplasmic phosphorylated ERK facilitates movement of ER-anchored calcium sensors to the PM. The driving force of trans-localization of calcium-dependent proteins enhances the contact between the activated EGFR and ER-localized phosphatase, PTP1B. Consequently, our findings suggest a mechanism underneath the facilitation of EGFR dephosphorylation by cytoplasmic PEA-15 expression inside TNBC cells, which may be one of the dynamic mechanisms for down-regulation of activated EGFR in cancer cells.

Original language	English
Pages (from-to)	1033-1039
Number of pages	7
Journal	FEBS Letters
Volume	589
Issue number	9
DOIs	https://doi.org/10.1016/j.febslet.2015.03.009
Publication status	Published - 2015 Apr 13

Keywords

EGFR dephosphorylation
ER-PM contact
PEA-15
PTP1B
Triple-negative breast cancer cells
pERK1/2

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.febslet.2015.03.009

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@article{3aeaf88519994983b2145291537d58fc,

title = "PEA-15 facilitates EGFR dephosphorylation via ERK sequestration at increased ER-PM contacts in TNBC cells",

abstract = "Phosphoprotein enriched in astrocytes of 15kDa (PEA-15) is known to sequester extracellular signal-regulated kinase (ERK) in the cytoplasm, inhibiting tumorigenesis of human breast cancer cells. Here, we describe how PEA-15 expression affects the dephosphorylation of epidermal growth factor receptor (EGFR) through endoplasmic reticulum (ER)-plasma membrane (PM) contacts in MDA-MB-468, triple-negative breast cancer (TNBC) cells. The increased intracellular calcium concentration resulting from increased cytoplasmic phosphorylated ERK facilitates movement of ER-anchored calcium sensors to the PM. The driving force of trans-localization of calcium-dependent proteins enhances the contact between the activated EGFR and ER-localized phosphatase, PTP1B. Consequently, our findings suggest a mechanism underneath the facilitation of EGFR dephosphorylation by cytoplasmic PEA-15 expression inside TNBC cells, which may be one of the dynamic mechanisms for down-regulation of activated EGFR in cancer cells.",

keywords = "EGFR dephosphorylation, ER-PM contact, PEA-15, PTP1B, Triple-negative breast cancer cells, pERK1/2",

author = "Miyoung Shin and Lee, {Kyung Eun} and Yang, {Eun Gyeong} and Hyesung Jeon and Song, {Hyun Kyu}",

note = "Funding Information: This work was supported by Grants from the National Research Foundation of Korea (NRF), funded by the Korean government (MSIP) ( NRF-2011-0028168 and NRF-2013R1A1A2020177 ). This study was also supported by the Intramural Research Program of the KIST, and a Korea University Grant. Publisher Copyright: {\textcopyright} 2015 Federation of European Biochemical Societies. All rights reserved.",

year = "2015",

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doi = "10.1016/j.febslet.2015.03.009",

language = "English",

volume = "589",

pages = "1033--1039",

journal = "FEBS Letters",

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T1 - PEA-15 facilitates EGFR dephosphorylation via ERK sequestration at increased ER-PM contacts in TNBC cells

AU - Shin, Miyoung

AU - Lee, Kyung Eun

AU - Yang, Eun Gyeong

AU - Jeon, Hyesung

AU - Song, Hyun Kyu

N1 - Funding Information: This work was supported by Grants from the National Research Foundation of Korea (NRF), funded by the Korean government (MSIP) ( NRF-2011-0028168 and NRF-2013R1A1A2020177 ). This study was also supported by the Intramural Research Program of the KIST, and a Korea University Grant. Publisher Copyright: © 2015 Federation of European Biochemical Societies. All rights reserved.

PY - 2015/4/13

Y1 - 2015/4/13

N2 - Phosphoprotein enriched in astrocytes of 15kDa (PEA-15) is known to sequester extracellular signal-regulated kinase (ERK) in the cytoplasm, inhibiting tumorigenesis of human breast cancer cells. Here, we describe how PEA-15 expression affects the dephosphorylation of epidermal growth factor receptor (EGFR) through endoplasmic reticulum (ER)-plasma membrane (PM) contacts in MDA-MB-468, triple-negative breast cancer (TNBC) cells. The increased intracellular calcium concentration resulting from increased cytoplasmic phosphorylated ERK facilitates movement of ER-anchored calcium sensors to the PM. The driving force of trans-localization of calcium-dependent proteins enhances the contact between the activated EGFR and ER-localized phosphatase, PTP1B. Consequently, our findings suggest a mechanism underneath the facilitation of EGFR dephosphorylation by cytoplasmic PEA-15 expression inside TNBC cells, which may be one of the dynamic mechanisms for down-regulation of activated EGFR in cancer cells.

AB - Phosphoprotein enriched in astrocytes of 15kDa (PEA-15) is known to sequester extracellular signal-regulated kinase (ERK) in the cytoplasm, inhibiting tumorigenesis of human breast cancer cells. Here, we describe how PEA-15 expression affects the dephosphorylation of epidermal growth factor receptor (EGFR) through endoplasmic reticulum (ER)-plasma membrane (PM) contacts in MDA-MB-468, triple-negative breast cancer (TNBC) cells. The increased intracellular calcium concentration resulting from increased cytoplasmic phosphorylated ERK facilitates movement of ER-anchored calcium sensors to the PM. The driving force of trans-localization of calcium-dependent proteins enhances the contact between the activated EGFR and ER-localized phosphatase, PTP1B. Consequently, our findings suggest a mechanism underneath the facilitation of EGFR dephosphorylation by cytoplasmic PEA-15 expression inside TNBC cells, which may be one of the dynamic mechanisms for down-regulation of activated EGFR in cancer cells.

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KW - ER-PM contact

KW - PEA-15

KW - PTP1B

KW - Triple-negative breast cancer cells

KW - pERK1/2

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PEA-15 facilitates EGFR dephosphorylation via ERK sequestration at increased ER-PM contacts in TNBC cells

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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