Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous cues, including amino acids, which promote mTORC1 translocation to the lysosomal surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form a signaling system that is necessary for amino acid sensing by mTORC1. Amino acids stimulate the binding of guanosine triphosphate to RagA and RagB but the factors that regulate Rag nucleotide loading are unknown. Here, we identify HBXIP and C7orf59 as two additional Ragulator components that are required for mTORC1 activation by amino acids. The expanded Ragulator has nucleotide exchange activity toward RagA and RagB and interacts with the Rag heterodimers in an amino acid- and v-ATPase-dependent fashion. Thus, we provide mechanistic insight into how mTORC1 senses amino acids by identifying Ragulator as a guanine nucleotide exchange factor (GEF) for the Rag GTPases.
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PMID:Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. 2298 Sep 80

LAMTOR3 (MP1) and LAMTOR2 (p14) form a heterodimer as part of the larger Ragulator complex that is required for MAPK and mTOR1 signaling from late endosomes/lysosomes. Here, we show that loss of LAMTOR2 (p14) results in an unstable cytosolic monomeric pool of LAMTOR3 (MP1). Monomeric cytoplasmic LAMTOR3 is rapidly degraded in a proteasome-dependent but lysosome-independent manner. Mutational analyses indicated that the turnover of the protein is dependent on ubiquitination of several lysine residues. Similarly, other Ragulator subunits, LAMTOR1 (p18), LAMTOR4 (c7orf59), and LAMTOR5 (HBXIP), are degraded as well upon the loss of LAMTOR2. Thus the assembly of the Ragulator complex is monitored by cellular quality control systems, most likely to prevent aberrant signaling at the convergence of mTOR and MAPK caused by a defective Ragulator complex.
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PMID:Stability of the endosomal scaffold protein LAMTOR3 depends on heterodimer assembly and proteasomal degradation. 2365 55

p18/LAMTOR1 is a membrane protein specifically localized to the surface of late endosomes/lysosomes that serves as an anchor for the "Ragulator" complex, which contains p14/LAMTOR2, MP1/LAMTOR3, HBXIP, and C7orf59. The Ragulator interacts with RagAB/CD GTPases and V-ATPase and plays crucial roles for activation of mammalian target of rapamycin complex 1 (mTORC1) on the lysosomal surface. Activated mTORC1 orchestrates various cellular functions, for example, macromolecule biosynthesis, energy metabolism, autophagy, cell growth, responses to growth factors, and the trafficking and maturation of lysosomes. The Ragulator can also regulate a branch of the MAPK pathway by recruiting MEK1 to MP1/LAMTOR3. These findings suggest that p18/LAMTOR1 creates a core platform for intracellular signaling pathways that function via late endosomes/lysosomes.
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PMID:p18/LAMTOR1: a late endosome/lysosome-specific anchor protein for the mTORC1/MAPK signaling pathway. 2437 28