The mTOR-signaling pathway in regulating metabolism and growth

¹ Center for Nutrition Modeling, Department of Animal and Poultry Science, University of Guelph, Guelph, ON, Canada N1G 2W1

^* To whom correspondence should be addressed. E-mail: yang{at}uoguelph.ca.

	Abstract

The mammalian target of rapamycin (mTOR) plays key roles in cellular metabolism, and hypertrophic-hyperplasic growth, and it acts as a central regulator of protein synthesis and ribosome biogenesis at transcriptional and translational levels by sensing and integrating signals from mitogens and nutrients. Hormonal and stress factors can affect the mTOR-signaling pathway via their receptors and signal transduction pathways. Nutritional regulations of the mTOR-signaling pathway are mediated by their corresponding plasma membrane transporters and(or) other unknown mechanisms. Adenine monophosphate activated protein kinase, an important cellular energy sensor, can interact with the mTOR signaling pathway to maintain cellular energy homeostasis. Interactions of mTOR with raptor or rictor result in two mTOR complexes with the former (mTOR complex-1) being the primary controller of cell growth and the latter (mTOR complex-2) mediating effects that are insensitive to rapamycin such as cytoskeletal organization. Upstream elements of the mTOR-signaling pathway include Ras-homolog enriched in brain, and tuberous sclerosis complex 1 and 2 (TSC1 and 2) with TSC2 as the linker between phosphatidylinositol 3-kinase / protein kinase B or Ras/Raf-mitogen-activated protein kinase/extracellular signal regulated protein kinase pathways and the mTOR pathway. Ribosomal protein S6 protein kinase 1 and eukaryotic initiation factor 4E binding protein 1 are currently the two best-known downstream effectors of mTOR signaling. Hormonal factors, stressors, and nutrients can differentially mediate cellular metabolism and growth via the mTOR pathway with effectors specific to organ or tissue types involved.

Key Words: Growth, mammalian target of rapamycin, metabolism

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