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 |
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Pages (from-to) | 1033-1039 |
Number of pages | 7 |
Journal | FEBS Letters |
Volume | 589 |
Issue number | 9 |
DOIs | |
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