TY - JOUR
T1 - Autophagy proteins regulate ERK phosphorylation
AU - Martinez-Lopez, Nuria
AU - Athonvarangkul, Diana
AU - Mishall, Priti
AU - Sahu, Srabani
AU - Singh, Rajat
N1 - Funding Information:
We thank Dr Ana Maria Cuervo for helpful suggestions, and Bindi Patel for help with electron microscopy. This work was supported by DK087776 (R.S.), AG043517 (R.S.), an Ellison Medical Foundation new scholar award (R.S.), and DK020541 to the Einstein Diabetes Research Center. D.A. is supported by NIH training grant 5T32GM728837.
PY - 2013
Y1 - 2013
N2 - 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
AB - 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
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U2 - 10.1038/ncomms3799
DO - 10.1038/ncomms3799
M3 - Article
C2 - 24240988
AN - SCOPUS:84888153445
SN - 2041-1723
VL - 4
JO - Nature communications
JF - Nature communications
M1 - 2799
ER -