Signal integration by mTORC1 coordinates nutrient input with biosynthetic output

By Christian C. Dibble, B. Manning. Nature Cell Biology, 2013

684 citations recorded by the source corpus.

Flux through metabolic pathways is inherently sensitive to the levels of specific substrates and products, but cellular metabolism is also managed by integrated control mechanisms that sense the nutrient and energy status of a cell or organism. The mechanistic target of rapamycin complex 1 (mTORC1), a protein kinase complex ubiquitous to eukaryotic cells, has emerged as a critical signalling node that links nutrient sensing to the coordinated regulation of cellular metabolism. Here, we discuss the role of mTORC1 as a conduit between cellular growth conditions and the anabolic processes that promote cell growth. The emerging network of signalling pathways through which mTORC1 integrates systemic signals (secreted growth factors) with local signals (cellular nutrients — amino acids, glucose and oxygen — and energy, ATP) is detailed. Our expanding understanding of the regulatory network upstream of mTORC1 provides molecular insights into the integrated sensing mechanisms by which diverse cellular signals converge to control cell physiology.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/674eff050a77a8bfe926b73ae6c26122dc2881d1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

Making new contacts: the mTOR network in metabolism and signalling crosstalk (2014, background): “This phosphorylation of ATG14 inhibits PtdIns3P production by the associated kinase VPS34 (REF.”
Fundamentals of cancer metabolism (2016, background): “Normal cells, upon stimulation by growth factors, activate phosphatidylinositol 3-kinase (PI3K) and its downstream pathways AKT and mammalian target of rapamycin (mTOR), thereby promoting a robust anabolic program involving increased glycolytic flux and fatty acid synthesis through activation of hyp”
The CASTOR proteins are arginine sensors for the mTORC1 pathway (2016, neutral): “A uthor M anuscript A uthor M anuscript growth controller that integrates diverse environmental inputs to coordinate many anabolic and catabolic processes in cells (Ban et al., 2004; Dibble and Manning, 2013; Efeyan et al., 2012; Hara, 1998).”
Phosphatidylinositol-5-phosphate 4-kinases regulate cellular lipid metabolism by facilitating autophagy (2018, background): “In particular, the amino acid arginine, a known activator of mTORC1 (Ban et al., 2004; Dibble and Manning, 2013; Efeyan et al., 2012; Hara et al., 1998), was remarkably decreased (Figure S1F).”
The Roles of Autophagy in Cancer (2018, background): “mTOR consists of two complexes, mTORC1 and mTORC2, each of which exhibits distinct functions and localization [23,24,25].”