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

Research output: Contribution to journalArticle

5 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 languageEnglish
Pages (from-to)1033-1039
Number of pages7
JournalFEBS Letters
Volume589
Issue number9
DOIs
Publication statusPublished - 2015 Apr 13

Fingerprint

Triple Negative Breast Neoplasms
Phosphoproteins
Extracellular Signal-Regulated MAP Kinases
Cell membranes
Epidermal Growth Factor Receptor
Astrocytes
Endoplasmic Reticulum
Cell Membrane
Cells
Calcium
Phosphoric Monoester Hydrolases
Carcinogenesis
Cytoplasm
Down-Regulation
Breast Neoplasms
Sensors
Neoplasms
Proteins

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 journalArticle

Shin, Miyoung ; Lee, Kyung Eun ; Yang, Eun Gyeong ; Jeon, Hyesung ; Song, Hyun Kyu. / PEA-15 facilitates EGFR dephosphorylation via ERK sequestration at increased ER-PM contacts in TNBC cells. In: FEBS Letters. 2015 ; Vol. 589, No. 9. pp. 1033-1039.
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