The amino acid sensitive TOR pathway from yeast to mammals

University of Cincinnati Genome Research Institute, 2180 East Galbraith Road, Cincinnati, OH 45237, USA.
FEBS Letters (Impact Factor: 3.17). 06/2006; 580(12):2821-9. DOI: 10.1016/j.febslet.2006.04.068
Source: PubMed


The target of rapamycin (TOR) is an ancient effector of cell growth that integrates signals from growth factors and nutrients. Two downstream effectors of mammalian TOR, the translational components S6K1 and 4EBP1, are commonly used as reporters of mTOR activity. The conical signaling cascade initiated by growth factors is mediated by PI3K, PKB, TSC1/2 and Rheb. However, the process through which nutrients, i.e., amino acids, activate mTOR remains largely unknown. Evidence exists for both an intracellular and/or a membrane bound sensor for amino acid mediated mTOR activation. Research in eukaryotic models, has implicated amino acid transporters as nutrient sensors. This review describes recent advances in nutrient signaling that impinge on mTOR and its targets including hVps34, class III PI3K, a transducer of nutrient availability to mTOR.

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    • "Several factors involved in amino acid - MTOR sig - naling have been described in the past and have been reviewed in detail elsewhere ( Dann and Thomas 2006 ; Avruch et al . 2009 ; Meijer and Codogno 2009 ; Kim and Guan 2011 ; Laplante and Sabatini 2012 ) ( Fig . 2 ) . "
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    ABSTRACT: Amino acids not only participate in intermediary metabolism but also stimulate insulin-mechanistic target of rapamycin (MTOR)-mediated signal transduction which controls the major metabolic pathways. Among these is the pathway of autophagy which takes care of the degradation of long-lived proteins and of the elimination of damaged or functionally redundant organelles. Proper functioning of this process is essential for cell survival. Dysregulation of autophagy has been implicated in the etiology of several pathologies. The history of the studies on the interrelationship between amino acids, MTOR signaling and autophagy is the subject of this review. The mechanisms responsible for the stimulation of MTOR-mediated signaling, and the inhibition of autophagy, by amino acids have been studied intensively in the past but are still not completely clarified. Recent developments in this field are discussed.
    Amino Acids 06/2014; 47(10). DOI:10.1007/s00726-014-1765-4 · 3.29 Impact Factor
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    • "Rapamycin is a specific inhibitor of mTOR (Dann and Thomas, 2006; Wullschleger et al., 2006). It inhibits mTOR by binding with high affinity to its internal receptor, FKBP12 [FK506-binding protein 12 (FK506 is an immunosuppressant macrolide)]. "
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    ABSTRACT: Oligodendrocyte development is controlled by numerous extracellular signals that regulate a series of transcription factors that promote the differentiation of oligodendrocyte progenitor cells to myelinating cells in the central nervous system. A major element of this regulatory system that has only recently been studied is the intracellular signaling from surface receptors to transcription factors to downregulate inhibitors and upregulate inducers of oligodendrocyte differentiation and myelination. The current review focuses on one such pathway: the mammalian target of rapamycin (mTOR) pathway, which integrates signals in many cell systems and induces cell responses including cell proliferation and cell differentiation. This review describes the known functions of mTOR as they relate to oligodendrocyte development, and its recently discovered impact on oligodendrocyte differentiation and myelination. A potential model for its role in oligodendrocyte development is proposed.
    ASN Neuro 02/2013; 5(1). DOI:10.1042/AN20120092 · 4.02 Impact Factor
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    • "In our present study, mTOR and its downstream effectors were elevated in DHEA-treated PCOS mouse model. The mTORC1 and mTORC2 have crucial roles in different pathways as energy and nutrient sensing, metabolism, cell growth, and differentiation [41-46]. We showed previously that mTOR is ubiquitously expressed in mouse ovary with predominantly cytoplasmic and perinuclear expression in granulosa cells. "
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder affecting 5-10 % of women in reproductive age that is characterized by hyperandrogenism, oligo- or anovulation and infertility. However the pathophysiology of PCOS still remains unknown. The mammalian target of rapamycin (mTOR) is a central component that regulates various processes including cell growth, proliferation, metabolism, and angiogenesis. mTOR signaling cascade has recently been examined in ovarian follicles where it regulates granulosa cell proliferation and differentiation. mTOR functions as two complexes, mTOR complex 1 and 2. Therefore, we hypothesized that mTORC1 and/or 2 may have important role in proliferation of theca and granulosa cells in PCOS. In the present study, we sought to determine the mTOR signaling pathway in PCOS mouse ovary. We designed 3 groups: Control (C, no treatment), PCOS (P, The injection of DHEA (6 mg/100 g BW in 0.1 ml of sesame oil) (s.c) for 20 consecutive days), Vehicle (V, daily (s.c) sesame oil alone injection). Our results showed that mTORC1 and mTORC2-mediated signaling may play a role in PCOS mouse ovary. These findings provide evidence that mTORC1 and mTORC2 may have responsibility in increased ovarian follicular cell proliferation and growth in PCOS. Consequently, these results suggest that the mTOR signaling pathways (mTORC1 and mTORC 2) may create new clinical strategies to optimize developmental competence of PCOS should target correction of the entire follicle growth, oocyte development process and anovulatory infertility in PCOS.
    Journal of Ovarian Research 11/2012; 5(1):38. DOI:10.1186/1757-2215-5-38 · 2.43 Impact Factor
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