Autophagy proteins regulate ERK phosphorylation

Nuria Martinez-Lopez, Diana Athonvarangkul, Priti L. Mishall, Srabani Sahu, Rajat Singh

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Autophagy is a conserved pathway that maintains cellular quality control. Extracellular signal-regulated kinase (ERK) controls various aspects of cell physiology including proliferation. Multiple signalling cascades, including ERK, have been shown to regulate autophagy, however whether autophagy proteins (ATG) regulate cell signalling is unknown. Here we show that growth factor exposure increases the interaction of ERK cascade components with ATG proteins in the cytosol and nucleus. ERK and its upstream kinase MEK localize to the extra-luminal face of autophagosomes. ERK2 interacts with ATG proteins via its substrate-binding domains. Deleting Atg7 or Atg5 or blocking LC3 lipidation or ATG5-ATG12 conjugation decreases ERK phosphorylation. Conversely, increasing LC3-II availability by silencing the cysteine protease ATG4B or acute trehalose exposure increases ERK phosphorylation. Decreased ERK phosphorylation in Atg5-/- cells does not occur from overactive phosphatases. Our findings thus reveal an unconventional function of ATG proteins as cellular scaffolds in the regulation of ERK phosphorylation.copyright

Original languageEnglish (US)
Article number2799
JournalNature Communications
Volume4
DOIs
StatePublished - 2013

Fingerprint

phosphorylation
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Autophagy
proteins
Proteins
cascades
cytology
Cell signaling
MAP Kinase Kinase Kinases
Cell Physiological Phenomena
protease
Trehalose
phosphatases
Cysteine Proteases
cysteine
Physiology
quality control
cells
conjugation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Martinez-Lopez, N., Athonvarangkul, D., Mishall, P. L., Sahu, S., & Singh, R. (2013). Autophagy proteins regulate ERK phosphorylation. Nature Communications, 4, [2799]. https://doi.org/10.1038/ncomms3799

Autophagy proteins regulate ERK phosphorylation. / Martinez-Lopez, Nuria; Athonvarangkul, Diana; Mishall, Priti L.; Sahu, Srabani; Singh, Rajat.

In: Nature Communications, Vol. 4, 2799, 2013.

Research output: Contribution to journalArticle

Martinez-Lopez, N, Athonvarangkul, D, Mishall, PL, Sahu, S & Singh, R 2013, 'Autophagy proteins regulate ERK phosphorylation', Nature Communications, vol. 4, 2799. https://doi.org/10.1038/ncomms3799
Martinez-Lopez, Nuria ; Athonvarangkul, Diana ; Mishall, Priti L. ; Sahu, Srabani ; Singh, Rajat. / Autophagy proteins regulate ERK phosphorylation. In: Nature Communications. 2013 ; Vol. 4.
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