Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms
Abstract
Amino acids are basic building blocks for all organisms and are essential for cell growth and proliferation. Cells use a set of protein machines to sense the availability of amino acids to carry out basic responses. In particular, the mTORC1 pathway is a central sensor of amino acids in mammalian cells. Residing on the lysosomal surface upon activation, mTORC1 processes signals from the upstream Rag GTPases and stimulates downstream effectors through phosphorylation cascades. Ragulator and SLC38A9 are key components of the lysosomal branch of the amino acid-sensing machinery upstream of the Rag GTPases, but how they regulate the Rag GTPases at the molecular level remains poorly understood. Here we used kinetic analyses to define their functions.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 04, 2018
- Source ID
- 10.1073/pnas.1811727115
Entities
People
- David M. Sabatini
- Kuang Shen
Organizations
- American Cancer Society
- Broad Institute
- Howard Hughes Medical Institute
- Koch Institute for Integrative Cancer Research at MIT
- Life Sciences Research Foundation
- Lustgarten Foundation for Pancreatic Cancer Research
- Massachusetts Institute of Technology
- National Institutes of Health
- United States Department of Defense
- Whitehead Institute