Title: PP2A(T61varepsilon) Is an Inhibitor of MAP4K3 in Nutrient Signaling to mTOR
Authors: Yan, Lijun
Mieulet, Virginie
Burgess, Darren
Findlay, Greg M
Sully, Katherine
Procter, Julia
Goris, Jozef
Janssens, Veerle
Morrice, Nick A
Lamb, Richard F # ×
Issue Date: Mar-2010
Publisher: Cell Press
Series Title: Molecular Cell vol:37 issue:5 pages:633-642
Abstract: The mammalian target of rapamycin (mTOR) pathway is activated by a variety of stimuli, including nutrients such as glucose and amino acids. The Ste20 family kinase MAP4K3 is regulated by amino acids and acts upstream of mTORC1. Here we investigate how MAP4K3 activity is regulated by amino acid sufficiency. We identify a transautophosphorylation site in the MAP4K3 kinase activation segment (Ser170) that is required for MAP4K3 activity and its activation of mTORC1 signaling. Following amino acid withdrawal, Ser170 is dephosphorylated via PP2A complexed to PR61varepsilon, a PP2A-targeting subunit. Inhibition of PR61varepsilon expression prevents MAP4K3 Ser170 dephosphorylation and impairs mTORC1 inhibition during amino acid withdrawal. We propose that during amino acid sufficiency Ser170-phosphorylated MAP4K3 activates mTORC1, but that upon amino acid restriction MAP4K3 preferentially interacts with PP2A(T61varepsilon), promoting dephosphorylation of Ser170, MAP4K3 inhibition, and, subsequently, inhibition of mTORC1 signaling.
ISSN: 1097-2765
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Protein Phosphorylation and Proteomics
× corresponding author
# (joint) last author

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