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This Article Full Text Full Text (PDF) All Versions of this Article: jas.2007-0567v1 86/14_suppl/E36    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yang, X. Articles by Fan, M. Z. PubMed PubMed Citation Articles by Yang, X. Articles by Fan, M. Z.

The mammalian target of rapamycin-signaling pathway in regulating metabolism and growth^1,2

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

³ Corresponding author: yang{at}uoguelph.ca

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 the 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 regulation of the mTOR-signaling pathway is mediated by their corresponding plasma membrane transporters, other unknown mechanisms, or both. 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 regulatory-associated protein of TOR or rapamycin-insensitive companion of mTOR result in 2 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, with tuberous sclerosis complex 2 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 2 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 the organ or tissue types involved.

Key Words: growth • mammalian target of rapamycin • metabolism