Mechanisms of amino acid sensing in mTOR signaling pathway
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Amino acids are fundamental nutrients for protein synthesis and cell growth (increase in cell size). Recently, many compelling evidences have shown that the level of amino acids is sensed by extra- or intra-cellular amino acids sensor(s) and regulates protein synthesis/degradation. Mammalian target of rapamycin complex 1 (mTORC1) is placed in a central position in cell growth regulation and dysregulation of mTOR signaling pathway has been implicated in many serious human diseases including cancer, diabetes, and tissue hypertrophy. Although amino acids are the most potent activator of mTORC1, how amino acids activate mTOR signaling pathway is still largely unknown. This is partly because of the diversity of amino acids themselves including structure and metabolism. In this review, current proposed amino acid sensing mechanisms to regulate mTORC1 and the evidences pro/against the proposed models are discussed.
Abstract
Amino acids are fundamental nutrients for protein synthesis and cell growth (increase in cell size). Recently, many compelling evidences have shown that the level of amino acids is sensed by extra- or intra-cellular amino acids sensor(s) and regulates protein synthesis/degradation. Mammalian target of rapamycin complex 1 (mTORC1) is placed in a central position in cell growth regulation and dysregulation of mTOR signaling pathway has been implicated in many serious human diseases including cancer, diabetes, and tissue hypertrophy. Although amino acids are the most potent activator of mTORC1, how amino acids activate mTOR signaling pathway is still largely unknown. This is partly because of the diversity of amino acids themselves including structure and metabolism. In this review, current proposed amino acid sensing mechanisms to regulate mTORC1 and the evidences pro/against the proposed models are discussed.
참고문헌 (81)
- Abraham RT, "Immunopharmacology of rapamycin", Annu Rev Immunol, 14, pp.483~510 (1996)
- Backer JM, "The regulation and function of Class III PI3Ks: novel roles for Vps34", Biochem J, 410, pp.1~17 (2008), .
- Bai X, "Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38", Science, 318, pp.977~980 (2007)
- Balage M, "Amino acids and insulin are both required to regulate assembly of the eIF4E. eIF4G complex in rat skeletal muscle", Am J Physiol, 281, pp.E565~574 (2001)
- Blommaart EF, "Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes", J Biol Chem, 270, pp.2320~2326 (1995)
- Brown EJ, "A mammalian protein targeted by G1-arresting rapamycin-receptor complex", Nature, 369, pp.756~758 (1994)
- Byfield MP, "hVps34 is a nutrientregulated lipid kinase required for activation of p70 S6 kinase", J Biol Chem, 280, pp.33076~33082 (2005)
- Chiu MI, "RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12", rapamycin complex, 1994, pp.91, 12574~12578
- Cruz MC, "Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans", Mol Cell Biol, 19, pp.4101~4112 (1999)
- Dennis PB, "Mammalian TOR: a homeostatic ATP sensor", Science, 294, pp.1102~1105 (2001)
- Dubouloz F, "The TOR and EGO protein complexes orchestrate microautophagy in yeast", Mol Cell, 19, pp.15~26 (2005)
- Facchinetti V, "The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C", EMBO J, 27, pp.1932~1943 (2008)
- Fahien LA, "Regulation of insulin release by factors that also modify glutamate dehydrogenase", J Biol Chem, 263, pp.13610~13614 (1988)
- Findlay GM, "A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling", Biochem J, 403, pp.13~20 (2007)
- Fingar DC, "Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1", eIF4E, 2002, pp.16, 1472~1487
- Gao M, "A conserved GTPase-containing complex is required for intracellular sorting of the general amino-acid permease in yeast", Nat Cell Biol, 8, pp.657~667 (2006)
- Garami A, "Insulin activation of Rheb, a mediator of mTOR", S6K, Mol Cell, pp.2003, 11[DOI]
- Garcia-Martinez JM, "mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serumand glucocorticoid-induced protein kinase 1 (SGK1)", Biocheml J, 416, pp.375~385 (2008)
- Garlick PJ, "Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin. Effect of branched-chain amino acids", Biochem J, 254, pp.579~584 (1988)
- Guertin DA, "Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1", Dev Cell, 11, pp.859~871 (2006)
- Guertin DA, "Defining the role of mTOR in cancer", Cancer cell, 12, pp.9~22 (2007)
- Gulati P, "Amino acids activate mTOR complex 1 via Ca2+", CaM signaling to hVps34, 2008, pp.7, 456~465
- Hall DJ, "Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila", BMC Biol, 5, pp.10~ (2007)
- Hara K, "Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action", Cell, 110, pp.177~189 (2002)
- Hara K, "Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism", J Biol Chem, 273, pp.14484~14494 (1998)
- Haussinger D, "The role of cellular hydration in the regulation of cell function", Biochem J, 313, pp.697~710 (1996)
- Hay N, "Upstream and downstream of mTOR", Genes Dev, 18, pp.1926~1945 (2004)
- Heitman J, "Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast", Science, 253, pp.905~909 (1991)
- Hsu YC, "Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase", Nature, 445, pp.785~788 (2007)
- Hyde R, "Amino acid transporters: roles in amino acid sensing and signalling in animal cells", Biochem J, 373, pp.1~18 (2003)
- Iiboshi Y, "Amino acid-dependent control of p70(s6k). Involvement of tRNA aminoacylation in the regulation", J Biol Chem, 274, pp.1092~1099 (1999)
- Ikenoue T, "Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling", EMBO J, 27, pp.1919~1931 (2008)
- Inoki K, "Dysregulation of the TSC-mTOR pathway in human disease", Nat Gene, 37, pp.19~24 (2005)
- Inoki K, "Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling", Genes Dev, 17, pp.1829~1834 (2003)
- Inoki K, "Signaling by target of rapamycin proteins in cell growth control", Microbiol Mol Biol Rev, 69, pp.79~100 (2005)
- Inoki K, "TSC2 mediates cellular energy response to control cell growth and survival", Cell, 115, pp.577~590 (2003)
- Jacinto E, "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive", Nat Cell Biol, 6, pp.1122~1128 (2004)
- Juhasz G, "The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila", J Cell Biol, 181, pp.655~666 (2008)
- Kim DH, "mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery", Cell, 110, pp.163~175 (2002)
- Kim DH, "GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR", Mol Cell, 11, pp.895~904 (2003)
- Kim E, "Regulation of TORC1 by Rag GTPases in nutrient response", Nat Cell Biol, 10, pp.935~945 (2008)
- Kim E, "RAG GTPases in nutrient-mediated TOR signaling pathway", Cell Cycle, 8 (2009)
- Lee CH, "mTOR pathway as a target in tissue hypertrophy", Annu Rev Pharmacol Toxicol, 47, pp.443~467 (2007)
- Lindmo K, "Regulation of membrane traffic by phosphoinositide 3-kinases", J Cell Sci, 119, pp.605~614 (2006)
- Loewith R, "Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control", Mol Cell, 10, pp.457~468 (2002)
- Long W, "Amino acids regulate skeletal muscle PHAS-I and p70 S6-kinase phosphorylation independently of insulin", Am J Physiol, 279, pp.E301~306 (2000)
- Long X, "Rheb binds and regulates the mTOR kinase", Curr Biol, 15, pp.702~713 (2005)
- Long X, "Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency", J Biol Chem, 280, pp.23433~23436 (2005)
- Lynch CJ, "Regulation of amino acid-sensitive TOR signaling by leucine analogues in adipocytes", J Cell Biochem, 77, pp.234~251 (2000)
- May ME, "Effects of branched-chain amino acids on protein turnover", Diabetes Metabol Rev, 5, pp.227~245 (1989)
- McDaniel ML, "Metabolic and autocrine regulation of the mammalian target of rapamycin by pancreatic beta-cells", Diabetes, 51, pp.2877~2885 (2002)
- Menand B, "Expression and disruption of the Arabidopsis TOR (target of rapamycin) gene", Proc Natl Acad Sci USA, 99, pp.6422~6427 (2002)
- Miotto G, "Control of hepatic proteolysis by leucine and isovaleryl-Lcarnitine through a common locus.Evidence for a possible mechanism of recognition at the plasma membrane.J Biol Chem", J Biol Chem, 267, pp.22066~22072 (1992)
- Miotto G, "Inhibition of macroautophagy and proteolysis in the isolated rat hepatocyte by a nontransportable derivative of the multiple antigen peptide Leu8-Lys4-Lys2-Lys-beta Ala", J Biol Chem, 269, pp.25348~25353 (1994)
- Nicklin P, "Bidirectional transport of amino acids regulates mTOR and autophagy", Cell, 136, pp.521~534 (2009)
- Nobukuni T, "Amino acids mediate mTOR", raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase, 2005, pp.102, 14238~14243
- Nobukuni T, "hvps34, an ancient player, enters a growing game: mTOR Complex1", S6K1 signaling, 2007, pp.19, 135~141
- Odorizzi G, "Phosphoinositide signaling and the regulation of membrane trafficking in yeast", Trends Biochem Sci, 25, pp.229~235 (2000)
- Oldham S, "Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin", Genes Dev, 14, pp.2689~2694 (2000)
- Oshiro N, "The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1", J Biol Chem, 282, pp.20329~20339 (2007)
- Pearce LR, "Identification of Protor as a novel Rictor-binding component of mTOR complex-2", Biochem J, 405, pp.513~522 (2007)
- Redpath NT, "Regulation of translation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway", EMBO J, 15, pp.2291~2297 (1996)
- Roccio M, "Regulation of the small GTPase Rheb by amino acids", Oncogene, 25, pp.657~664 (2006)
- Sabatini DM, "RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs", Cell, 78, pp.35~43 (1994)
- Sancak Y, "PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase", Mol Cell, 25, pp.903~915 (2007)
- Sancak Y, "The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1", Science, 320, pp.1496~1501 (2008)
- Sarbassov DD, "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton", Curr Biol, 14, pp.1296~1302 (2004)
- Saucedo LJ, "Rheb promotes cell growth as a component of the insulin", TOR signalling network, 2003, pp.5, 566~571
- Schmelzle T, "TOR, a central controller of cell growth", Cell, 103, pp.253~262 (2000)
- Sener A, "L-leucine and a nonmetabolized analogue activate pancreatic islet glutamate dehydrogenase", Nature, 288, pp.187~189 (1980)
- Shah OJ, "4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle", Am J Physiol, 279, pp.E715~729 (2000)
- Shintani T, "Autophagy in health and disease:a double-edged sword", Science, 306, pp.990~995 (2004)
- Smith EM, "The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses", J Biol Chem, 280, pp.18717~18727 (2005)
- Tee AR, "Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb", Curr Biol, 13, pp.1259~1268 (2003)
- Vander Haar E, "Insulin signalling to mTOR mediated by the Akt", PKB substrate PRAS40, 2007, pp.9, 316~323
- Wang L, "PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding", J Biol Chem, 282, pp.20036~20044 (2007)
- Xu G, "Metabolic regulation by leucine of translation initiation through the mTOR-signaling pathway by pancreatic beta-cells", Diabetes, 50, pp.353~360 (2001)
- Yan Y, "Regulation of class III (Vps34) PI3Ks", Biochem Soc Trans, 35, pp.239~241 (2007)
- Yan Y, "hVps15, but not Ca(2+)", CaM, is required for the activity and regulation of hVps34 in mammalian cells, 2009, pp.417, 747~755
- Yang Q, "Expanding mTOR signaling", Cell Res, 17, pp.666~681 (2007)
- Zhang Y, "Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins", Nat Cell Biol, 5, pp.578~581 (2003)
