[1] HEITMAN J,MOVVA N R,HALL M N.Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast[J].Science,1991,253:905-909.
[2] AVRUCH J,LONG X,ORTIZ-VEGA S,et al.Amino acid regulation of TOR complex 1[J].Amrican Journal of Physiology:Endocrinology of Metabolism,2009,296(4):E592-E602.
[3] KIM J,GUAN K L.Amino acid signaling in TOR activation[J].Annual Review of Biochemistry,2011,80:1001-1032.
[4] SOULARD A,COHEN A,HALL M N.TOR signaling in invertebrates[J].Current Opinion in Cell Biology,2009,21(6):825-836.
[5] WULLSCHLEGER S,LOEWITH R,HALL M N.TOR signaling in growth and metabolism[J].Cell,2006,124(3):471-484.
[6] ZONCU R,EFEYAN A,SABATINI D M.mTOR:from growth signal integration to cancer,diabetes and ageing[J].Nature Reviews:Molecular Cell Biology,2011,12(1):21-35.
[7] BISCHOFF F,MOLENDIJK A,RAJENDRAKUMAR C S,et al.GTP-binding proteins in plants[J].Cellular and Molecular Life Sciences,1999,55(2):233-256.
[8] PADUCH M,JELEN F,OTLEWSKI J.Structure of small G proteins and their regulators[J].Acta Biochimica Polonica,2001,48(4):829-850.
[9] TAKAI Y,SASAKI T,MATOZAKI T.Small GTP-binding proteins[J].Physiological Reviews,2001,81(1):153-208.
[10] BOURNE H R,SANDERS D A,MCCORMICK F.The GTPase superfamily:conserved structure and molecular mechanism[J].Nature,1991,349:117-127.
[11] YANG Z.Small GTPase:versatile signaling switches in plants[J].The Plant Cell,2002,14:S375-S388.
[12] SARBASSOV D D,ALI S M,SENGUPTA S,et al.Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB[J].Molecular Cell,2006,22(2):159-168.
[13] CHOO A Y,BLENIS J.Not all substrates are treated equally:implications for mTOR,rapamycin-resistance and cancer therapy[J].Cell Cycle,2009,8(4):567-572.
[14] DOWLING R J,TOPISIROVIC I,ALAIN T,et al.mTORC1-mediated cell proliferation,but not cell growth,controlled by the 4E-BPs[J].Science,2010,328:1172-1176.
[15] PETERSON T R,SENGUPTA S S,HARRIS T E,et al.mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway[J].Cell,2011,146(3):408-420.
[16] PETERSON T R,LAPLANTE M,THOREEN C C,et al.DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival[J].Cell,2009,137(5):873-886.
[17] SANCAK Y,THOREEN C C,PETERSON T R,et al.PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase[J].Molecular Cell,2007,25(6):903-915.
[18] THEDIECK K,POLAK P,KIM M L,et al.PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis[J].PLoS One,2007,2(11):e1217.
[19] VANDER HAAR E,LEE S I,BANDHAKAVI S,et al.Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40[J].Nature Cell Biology,2007,9(3):316-323.
[20] SANCAK Y,PETERSON T R,SHAUL Y D,et al.The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1[J].Science,2008,320:1496-1501.
[21] GULATI P,GASPERS L D,DANN S G,et al.Amino acids activate mTOR complex 1 via Ca
2+/CaM signaling to hVps34[J].Cell Metabolism,2008,7(5):456-465.
[22] FINDLAY G M,YAN L,PROCTER J,et al.A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling[J].The Biochemical Journal,2007,403(1):13-20.
[23] YAN L,MIEULET V,BURGESS D,et al.PP2A T61 epsilon is an inhibitor of MAP4K3 in nutrient signaling to mTOR[J].Molecular Cell,2010,37(5):633-642.
[24] ZINZALLA V,STRACKA D,OPPLIGER W,et al.Activation of mTORC2 by association with the ribosome[J].Cell,2011,144(5):757-768.
[25] CYBULSKI N,HALL M N.TOR complex 2:a signaling pathway of its own[J].Trends in Biochemical Sciences,2009,34(12):620-627.
[26] YAMAGATA K,SANDERS L K,KAUFMANN W E,et al.Rheb,a growth factor-and synaptic activity-regulated gene,encodes a novel Ras-related protein[J].The Journal of Biological Chemistry,1994,269(23):16333-16339.
[27] YEE W M,WORLEY P F.Rheb interacts with Raf 1 kinase and may function to integrate growth factor-and protein kinase A dependent signals[J].Molecular and Cellular Biology,1997,17(2):921-933.
[28] PATEL P H,THAPAR N,GUO L,et al.Drosophila Rheb GTPase is required for cell cycle progression and cell growth[J].Journal of Cell Science,2003,116:3601-3610.
[29] LONG X,LIN Y,ORTIZ-VEGA S,et al.Rheb binds and regulates the mTOR kinase[J].Current Biology,2005,15(8):702-713.
[30] SUBRAMANIAM S,NAPOLITANO F,MEALER R G,et al.Rhes,a striatal-enriched small G protein,mediates Mtor signaling and L-DOPA-induced dyskinesia[J].Nature Neuroscience,2011,15(2):191-193.
[31] CAI S L,TEE A R,SHORT J D,et al.Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning[J].The Journal of Cell Biology,2006,173(2):279-289.
[32] YOSHIDA S,HONG S,SUZUKI T,et al.Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway[J].The Journal of Biological Chemistry,2011,286(37):32651-32660.
[33] SUN Y,FANG Y,YOON M S,et al.Phospholipase D1 is an effector of Rheb in the mTOR pathway[J].Proceedings of the National Academy of Sciences of the USA,2008,105(24):8286-8291.
[34] YOON M S,DU G,BACKER J M,et al.Class Ⅲ PI 3 kinase activates phospholipase D in an amino acid-sensing mTORC1 pathway[J].The Journal of Cell Biology,2011,195(3):435-447.
[35] BAI X,MA D,LIU A,et al.Rheb activates mTOR by antagonizing its endogenous inhibitor,FKBP38[J].Science,2007,318:977-980.
[36] DUNLOP E A,DODD K M,SEYMOUR L A,et al.Mammalian target of rapamycin complex 1-mediated phosphorylation of eukaryotic initiation factor 4E-binding protein 1 requires multiple protein-protein interactions for substrate recognition[J].Cellular Signalling,2009,21(7):1073-1084.
[37] ZHENG M,WANG Y H,WU X N,et al.Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy depletion induced suppression of mTORC1[J].Nature Cell Biology,2011,13(3):263-272.
[38] LI Y,INOKI K,VACRATSIS P,et al.The p38 and MK2 kinase cascade phosphorylates tuberin,the tuberous sclerosis 2 gene product,and enhances its interaction with 14 3 3[J].The Journal of Biological Chemistry,2003,278(16):13663-13671.
[39] WU X N,WANG X K,WU S Q,et al.Phosphorylation of Raptor by p38β participates in arsenite-induced mammalian target of rapamycin complex 1 (mTORC1) activation[J].The Journal of Biological Chemistry,2011,286(36):31501-31511.
[40] SEKIGUCHI T,HIROSE E,NAKASHIMA N,et al.Novel G proteins,Rag C and Rag D,interact with GTP-binding proteins,Rag A and Rag B[J].The Journal of Biological Chemistry,2001,276(10):7246-7257.
[41] HIROSE E,NAKASHIMA N,SEKIGUCHI T,et al.RagA is a functional homologue of
S.cerevisiae Gtr1p involved in the Ran/Gsp1-GTPase pathway[J].Journal of Cell Science,1998,111(Pt.1):11-21.
[42] SANCAK Y,BAR-PELED L,ZONCU R,et al.Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids[J].Cell,2010,141(2):290-303.
[43] DURAN A,AMANCHY R,LINARES J F,et al.p62 is a key regulator of nutrient sensing in the mTORC1 pathway[J].Molecular Cell,2011,44(1):134-146.
[44] KIM E,GORAKSHA-HICKS P,LI L,et al.Regulation of TORC1 by Rag GTPases in nutrient response[J].Nature Cell Biology,2008,10(8):935-945.
[45] BAR-PELED L,SCHWEITZER L D,ZONCU R,et al.Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1[J].Cell,2012,150(6):1196-208.
[46] HAN J M,JEONG S J,PARK M C,et al.Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway[J].Cell,2012,149(2):410-424.
[47] FANG Y,VILELLA-BACH M,BACHMANN R,et al.Phosphatidic acid-mediated mitogenic activation of mTOR signaling[J].Science,2001,294:1942-1945.
[48] MAEHAMA T,TANAKA M,NISHINA H,et al.RalA functions as an indispensable signal mediator for the nutrient-sensing system[J].The Journal of Biological Chemistry,2008,283(50):35053-35059.
[49] XU L,SALLOUM D,MEDLIN P S,et al.Phospholipase D mediates nutrient input to mammalian target of rapamycin complex 1(mTORC1)[J].The Journal of Biological Chemistry,2011,286(29):25477-25486.
[50] XU L,FRANKEL P,JACKSON D,et al.Elevated phospholipase D activity in H Ras but not K Ras transformed cells by the synergistic action of RalA and ARF6[J].Molecular and Cellular Biology,2003,23(2):645-654.
[51] LIU L,LUO Y,CHEN L,et al.Rapamycin inhibits cytoskeleton reorganization and cell motility by suppressing RhoA expression and activity[J].The Journal of Biological Chemistry,2010,285(49):38362-38373.
[52] LEE S E,SUN S C,CHOI H Y,et al.mTOR is required for asymmetric division through small GTPases in mouse oocytes[J].Molecular Reproduction and development,2012,79(5):356-366.
[53] GULHATI P,BOWEN K A,LIU J,et al.mTORC1 and mTORC2 regulate EMT,motility,and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways[J].Cancer Research,2011,71(9):3246-3256.
[54] GANGOITI P,ARANA L,OURO A,et al.Activation of mTOR and RhoA is a major mechanism by which Ceramide 1-phosphate stimulates macrophage proliferation[J].Cellular Signalling,2011,23(1):27-34.
[55] HALL A.Rho GTPases and the actin cytoskeleton[J].Science,1998,279:509-514.
[56] HERNANDEZ-NEGRETE I,CARRETERO-ORTEGA J,ROSENFELDT H,et al.P Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration[J].The Journal of Biological Chemistry,2007,282(32):23708-23715.
[57] JACINTO E,LOEWITH R,SCHMIDT A,et al.Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive[J].Nature Cell Biology,2004,6(11):1122-1128.
[58] SACI A,CANTLEY L C,CARPENTER C L.Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size[J].Molecular Cell,2011,42(1):50-61.
[59] ASLAN J E,MCCARTY O J.Regulation of the mTOR-Rac1 axis in platelet function[J].Small GTPases,2012,3(1):67-70.
[60] LI L,KIM E,YUAN H,et al.Regulation of mTORC1 by the Rab and Arf GTPases[J].The Journal of Biological Chemistry,2010,285(26):19705-19709.
[61] BRIDGES D,FISHER K,ZOLOV S N,et al.Rab5 proteins regulate activation and localization of target of rapamycin complex 1[J].The Journal of Biological Chemistry,2012,287(25):20913-20921.
[62] TATEBE H,MORIGASAKI S,MURAYAMA S,et al.Rab-family GTPase regulates TOR complex 2 signaling in fission yeast[J].Current Biology,2010,20(22):1975-1982.
[63] BERNDT N,HAMILTON A D,SEBTI S M.Targeting protein prenylation for cancer therapy[J].Nature Reviews Cancer,2011,11(11):775-791.
[64] DAZERT E,HALL M N.mTOR signaling in disease[J].Current Opinion in Cell Biology,2011,23(6):744-755.
[65] SCIARRETTA S,ZHAI P,SHAO D,et al.Rheb is a critical regulator of autophagy during myocardial ischemia:pathophysiological implications in obesity and metabolic syndrome[J].Circulation,2012,125(9):1134-1146.
[66] KOBAYASHI T,SHIMIZU Y,TERADA N,et al.Regulation of androgen receptor transactivity and mTOR-S6 kinase pathway by Rheb in prostate cancer cell proliferation[J].The Prostate,2010,70(8):866-874.
[67] PICCONI B,CALABRESI P.Rhes-mTORC1 interaction:a new possible therapeutic target in Parkinson’s disease and L-dopa-induced dyskinesia[J].Movement Disorders,2012,27(7):815.
