RagC Phosphorylation Autoregulates MTOR Complex 1

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2018 Dec 16

PMID 30552228

Citations 16

Authors

Guang Yang

Sean J Humphrey

Danielle S Murashige

Deanne Francis

Qiao-Ping Wang

Kristen C Cooke

G Gregory Neely

David E James

Affiliations

Soon will be listed here.

Abstract

The mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) controls cell growth, proliferation, and metabolism in response to diverse stimuli. Two major parallel pathways are implicated in mTORC1 regulation including a growth factor-responsive pathway mediated via TSC2/Rheb and an amino acid-responsive pathway mediated via the Rag GTPases. Here, we identify and characterize three highly conserved growth factor-responsive phosphorylation sites on RagC, a component of the Rag heterodimer, implicating cross talk between amino acid and growth factor-mediated regulation of mTORC1. We find that RagC phosphorylation is associated with destabilization of mTORC1 and is essential for both growth factor and amino acid-induced mTORC1 activation. Functionally, RagC phosphorylation suppresses starvation-induced autophagy, and genetic studies in reveal that RagC phosphorylation plays an essential role in regulation of cell growth. Finally, we identify mTORC1 as the upstream kinase of RagC on S21. Our data highlight the importance of RagC phosphorylation in its function and identify a previously unappreciated auto-regulatory mechanism of mTORC1 activity.

Citing Articles

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