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 | |
| Publication status | Published - 2015 Apr 13 |
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Keywords
- EGFR dephosphorylation
- ER-PM contact
- PEA-15
- pERK1/2
- PTP1B
- Triple-negative breast cancer cells
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Genetics
- Molecular Biology
- Structural Biology
- Medicine(all)
Cite this
PEA-15 facilitates EGFR dephosphorylation via ERK sequestration at increased ER-PM contacts in TNBC cells. / Shin, Miyoung; Lee, Kyung Eun; Yang, Eun Gyeong; Jeon, Hyesung; Song, Hyun Kyu.
In: FEBS Letters, Vol. 589, No. 9, 13.04.2015, p. 1033-1039.Research output: Contribution to journal › Article
}
TY - JOUR
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
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.
KW - EGFR dephosphorylation
KW - ER-PM contact
KW - PEA-15
KW - pERK1/2
KW - PTP1B
KW - Triple-negative breast cancer cells
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U2 - 10.1016/j.febslet.2015.03.009
DO - 10.1016/j.febslet.2015.03.009
M3 - Article
VL - 589
SP - 1033
EP - 1039
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 9
ER -