Amino acid signalling upstream of mTOR
TLDR
A model has emerged whereby mTORC1 activation occurs at the lysosome and is mediated through an amino acid sensing cascade involving RAG GTPases, Ragulator and vacuolar H+-ATPase (v- ATPase).Abstract:
Mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that is part of mTOR complex 1 (mTORC1), a master regulator that couples amino acid availability to cell growth and autophagy. Multiple cues modulate mTORC1 activity, such as growth factors, stress, energy status and amino acids. Although amino acids are key environmental stimuli, exactly how they are sensed and how they activate mTORC1 is not fully understood. Recently, a model has emerged whereby mTORC1 activation occurs at the lysosome and is mediated through an amino acid sensing cascade involving RAG GTPases, Ragulator and vacuolar H(+)-ATPase (v-ATPase).read more
Citations
More filters
Journal ArticleDOI
mTOR: a pharmacologic target for autophagy regulation
Young Chul Kim,Kun-Liang Guan +1 more
TL;DR: An overview of the mTOR signaling pathway, the mechanisms of m TOR in autophagy regulation, and the clinical implications of mTOR inhibitors in disease treatment are provided.
Journal ArticleDOI
Making new contacts: the mTOR network in metabolism and signalling crosstalk
TL;DR: Emerging evidence provides new insight into the control of mTOR by other pathways such as Hippo, WNT and Notch signalling, and this progress has expanded the list of downstream effectors and upstream regulators of m TOR signalling.
Journal ArticleDOI
Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1
Shuyu Wang,Zhi-Yang Tsun,Rachel L. Wolfson,Kuang Shen,Gregory A. Wyant,Molly Plovanich,Elizabeth D. Yuan,Tony D. Jones,Lynne Chantranupong,William C. Comb,Timothy C. Wang,Liron Bar-Peled,Roberto Zoncu,Christoph Straub,Choah Kim,Jiwon Park,Bernardo L. Sabatini,David M. Sabatini +17 more
TL;DR: SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, is identified as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases and Ragulator in an amino acid–sensitive fashion and is an excellent candidate for being an arginine sensor for the mTORC1 pathway.
Journal ArticleDOI
Regulation of mTORC1 by amino acids
TL;DR: The mechanistic target of rapamycin complex I (mTORC1) is a central regulator of cellular and organismal growth, and hyperactivation of this pathway is implicated in the pathogenesis of many human diseases including cancer and diabetes as discussed by the authors.
Journal ArticleDOI
Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation.
Mako Nakaya,Yichuan Xiao,Xiaofei Zhou,Jae Hoon Chang,Mikyoung Chang,Xuhong Cheng,Marzenna Blonska,Xin Lin,Shao Cong Sun,Shao Cong Sun +9 more
TL;DR: Findings highlight a mechanism of T cell activation involving ASCT2-dependent integration of the TCR signal and a metabolic signaling pathway that is independent of IKK kinase, a major downstream target of the CARMA1 complex.
References
More filters
mTOR Signaling in Growth Control and Disease
TL;DR: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis as mentioned in this paper, and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration.
Journal ArticleDOI
mTOR signaling in growth control and disease.
TL;DR: Recent advances in understanding of the mTOR pathway are reviewed and pharmacological approaches to treat human pathologies linked to mTOR deregulation are discussed.
Journal ArticleDOI
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
TL;DR: A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.
Journal ArticleDOI
Autophagy: Renovation of Cells and Tissues
Noboru Mizushima,Masaaki Komatsu +1 more
TL;DR: It is explored how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease.
Journal ArticleDOI
mTOR: from growth signal integration to cancer, diabetes and ageing
TL;DR: Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt.