MTOR: Difference between revisions
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Rapamycin arrested fungal activity at the [[G1 phase]] of the cell cycle. In rats, it suppressed the immune system by blocking the G1 to S phase transition in [[T-lymphocytes]].<ref name="pmid22168436">{{cite journal |author=Magnuson B, Ekim B, Fingar DC |title=Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks |journal=Biochem. J. |volume=441 |issue=1 |pages=1–21 |year=2012 |month=January |pmid=22168436 |doi=10.1042/BJ20110892 |url=}}</ref> In humans, it is used as an [[immunosuppressant]] following organ transplantation.<ref name="pmid8717522">{{cite journal |author=Abraham RT, Wiederrecht GJ |title=Immunopharmacology of rapamycin |journal=Annu. Rev. Immunol. |volume=14 |issue= |pages=483–510 |year=1996 |pmid=8717522 |doi=10.1146/annurev.immunol.14.1.483 |url=}}</ref> |
Rapamycin arrested fungal activity at the [[G1 phase]] of the cell cycle. In rats, it suppressed the immune system by blocking the G1 to S phase transition in [[T-lymphocytes]].<ref name="pmid22168436">{{cite journal |author=Magnuson B, Ekim B, Fingar DC |title=Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks |journal=Biochem. J. |volume=441 |issue=1 |pages=1–21 |year=2012 |month=January |pmid=22168436 |doi=10.1042/BJ20110892 |url=}}</ref> In humans, it is used as an [[immunosuppressant]] following organ transplantation.<ref name="pmid8717522">{{cite journal |author=Abraham RT, Wiederrecht GJ |title=Immunopharmacology of rapamycin |journal=Annu. Rev. Immunol. |volume=14 |issue= |pages=483–510 |year=1996 |pmid=8717522 |doi=10.1146/annurev.immunol.14.1.483 |url=}}</ref> |
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[[Saccharomyces cerevisiae]] can develop resistance to rapamycin, when one of three genes is knocked out.<ref name="pmid1715094">{{cite journal |author=Heitman J, Movva NR, Hall MN |title=Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast |journal=Science |volume=253 |issue=5022 |pages=905–9 |year=1991 |month=August |pmid=1715094 |doi= 10.1126/science.1715094|url=}}</ref> Two of the genes were called targets of rapamycin (TOR). The third gene was already known as Fpr1. Fpr1 is the ortholog of FKBP12 binding protein in the TOR complexes.<ref name="pmid20231296">{{cite journal |author=Foster KG, Fingar DC |title=Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony |journal=J. Biol. Chem. |volume=285 |issue=19 |pages=14071–7 |year=2010 |month=May |pmid=20231296 |pmc=2863215 |doi=10.1074/jbc.R109.094003 |url=}}</ref> In 1994, the mammalian target of rapamycin (mTOR) was identified as the rapamycin target in mammals by [[David M. Sabatini]] and [[Solomon H. Snyder]] (Johns Hopkins University)<ref name="pmid7518356">{{cite journal | author = Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH | title = RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs | journal = Cell | volume = 78 | issue = 1 | pages = 35–43 | year = 1994 | month = July | pmid = 7518356 | doi = 10.1016/0092-8674(94)90570-3 }}</ref> and [[Stuart L. Schreiber]] (Harvard University).<ref name="pmid8008069">{{cite journal |author=Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL |title=A mammalian protein targeted by G1-arresting rapamycin-receptor complex |journal=Nature |volume=369 |issue=6483 |pages=756–8 |year=1994 |month=June |pmid=8008069 |doi=10.1038/369756a0 |url=}}</ref> |
''[[Saccharomyces cerevisiae]]'' can develop resistance to rapamycin, when one of three genes is knocked out.<ref name="pmid1715094">{{cite journal |author=Heitman J, Movva NR, Hall MN |title=Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast |journal=Science |volume=253 |issue=5022 |pages=905–9 |year=1991 |month=August |pmid=1715094 |doi= 10.1126/science.1715094|url=}}</ref> Two of the genes were called targets of rapamycin (TOR). The third gene was already known as Fpr1. Fpr1 is the ortholog of FKBP12 binding protein in the TOR complexes.<ref name="pmid20231296">{{cite journal |author=Foster KG, Fingar DC |title=Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony |journal=J. Biol. Chem. |volume=285 |issue=19 |pages=14071–7 |year=2010 |month=May |pmid=20231296 |pmc=2863215 |doi=10.1074/jbc.R109.094003 |url=}}</ref> In 1994, the mammalian target of rapamycin (mTOR) was identified as the rapamycin target in mammals by [[David M. Sabatini]] and [[Solomon H. Snyder]] (Johns Hopkins University)<ref name="pmid7518356">{{cite journal | author = Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH | title = RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs | journal = Cell | volume = 78 | issue = 1 | pages = 35–43 | year = 1994 | month = July | pmid = 7518356 | doi = 10.1016/0092-8674(94)90570-3 }}</ref> and [[Stuart L. Schreiber]] (Harvard University).<ref name="pmid8008069">{{cite journal |author=Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL |title=A mammalian protein targeted by G1-arresting rapamycin-receptor complex |journal=Nature |volume=369 |issue=6483 |pages=756–8 |year=1994 |month=June |pmid=8008069 |doi=10.1038/369756a0 |url=}}</ref> |
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==Function== |
==Function== |
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mTOR integrates the input from upstream pathways, including [[insulin]], [[growth factors]] (such as [[IGF-1]] and [[IGF-2]]), and [[amino acid]]s.<ref name=Hay/> mTOR also senses cellular nutrient, oxygen, and energy levels.<ref name=Tok>{{cite journal |author=Tokunaga C, Yoshino K, Yonezawa K |title=mTOR integrates amino acid- and energy-sensing pathways |journal=Biochem Biophys Res Commun |volume=313 |issue=2 |pages=443–6 |year=2004 |pmid=14684182 |doi=10.1016/j.bbrc.2003.07.019}}</ref> The mTOR pathway is dysregulated in human diseases, such as [[diabetes]], [[obesity]], [[Depression (mood)|depression]], and certain [[cancer]]s.<ref name=Beevers/> [[Rapamycin]] is a bacterial product that can inhibit mTOR by associating with its intracellular receptor [[FKBP|FKBP12]].<ref name=Huang2001>{{cite journal |author=Huang S, Houghton P |title=Mechanisms of resistance to rapamycins |journal=Drug Resist Updat |volume=4 |issue=6 |pages=378–91 |year=2001 |pmid=12030785 |doi=10.1054/drup.2002.0227}}</ref><ref name=Huang2003>{{cite journal |author=Huang S, Bjornsti M, Houghton P |title=Rapamycins: mechanism of action and cellular resistance |journal=Cancer Biol Ther |volume=2 |issue=3 |pages=222–32 |year=2003 |pmid=12878853}}</ref> The [[FKBP|FKBP12]]-[[rapamycin]] complex binds directly to the FKBP12-Rapamycin Binding (FRB) domain of mTOR, inhibiting its activity.<ref name=Huang2003/> |
mTOR integrates the input from upstream pathways, including [[insulin]], [[growth factors]] (such as [[IGF-1]] and [[IGF-2]]), and [[amino acid]]s.<ref name=Hay/> mTOR also senses cellular nutrient, oxygen, and energy levels.<ref name=Tok>{{cite journal |author=Tokunaga C, Yoshino K, Yonezawa K |title=mTOR integrates amino acid- and energy-sensing pathways |journal=Biochem Biophys Res Commun |volume=313 |issue=2 |pages=443–6 |year=2004 |pmid=14684182 |doi=10.1016/j.bbrc.2003.07.019}}</ref> The mTOR pathway is dysregulated in human diseases, such as [[diabetes]], [[obesity]], [[Depression (mood)|depression]], and certain [[cancer]]s.<ref name=Beevers/> [[Rapamycin]] is a bacterial product that can inhibit mTOR by associating with its intracellular receptor [[FKBP|FKBP12]].<ref name=Huang2001>{{cite journal |author=Huang S, Houghton P |title=Mechanisms of resistance to rapamycins |journal=Drug Resist Updat |volume=4 |issue=6 |pages=378–91 |year=2001 |pmid=12030785 |doi=10.1054/drup.2002.0227}}</ref><ref name=Huang2003>{{cite journal |author=Huang S, Bjornsti M, Houghton P |title=Rapamycins: mechanism of action and cellular resistance |journal=Cancer Biol Ther |volume=2 |issue=3 |pages=222–32 |year=2003 |pmid=12878853}}</ref> The [[FKBP|FKBP12]]-[[rapamycin]] complex binds directly to the FKBP12-Rapamycin Binding (FRB) domain of mTOR, inhibiting its activity.<ref name=Huang2003/> |
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mTOR stands for mammalian Target Of Rapamycin and was named based on the precedent that TOR was first discovered via genetic and molecular studies of rapamycin-resistant mutants of [[Saccharomyces cerevisiae]] that identified FKBP12, Tor1, and Tor2 as the targets of rapamycin and provided robust support that the FKBP12-rapamycin complex binds to and inhibits the cellular functions of Tor1 and Tor2. |
mTOR stands for mammalian Target Of Rapamycin and was named based on the precedent that TOR was first discovered via genetic and molecular studies of rapamycin-resistant mutants of ''[[Saccharomyces cerevisiae]]'' that identified FKBP12, Tor1, and Tor2 as the targets of rapamycin and provided robust support that the FKBP12-rapamycin complex binds to and inhibits the cellular functions of Tor1 and Tor2. |
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==Complexes== |
==Complexes== |
Revision as of 09:27, 7 October 2013
Template:PBB The mammalian target of rapamycin (mTOR), also known as mechanistic target of rapamycin or FK506 binding protein 12-rapamycin associated protein 1 (FRAP1), is a protein that in humans is encoded by the MTOR gene.[1][2] mTOR is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription.[3][4] mTOR belongs to the phosphatidylinositol 3-kinase-related kinase protein family.
Discovery and history
mTOR is the mammalian target of rapamycin. Rapamycin was discovered in a soil sample from Easter Island, known locally as Rapa Nui, in the 1970s.[5] In that sample, the bacterium Streptomyces hygroscopicus made an antifungal, which researchers named rapamycin after the island. [6]
Rapamycin arrested fungal activity at the G1 phase of the cell cycle. In rats, it suppressed the immune system by blocking the G1 to S phase transition in T-lymphocytes.[7] In humans, it is used as an immunosuppressant following organ transplantation.[8]
Saccharomyces cerevisiae can develop resistance to rapamycin, when one of three genes is knocked out.[9] Two of the genes were called targets of rapamycin (TOR). The third gene was already known as Fpr1. Fpr1 is the ortholog of FKBP12 binding protein in the TOR complexes.[10] In 1994, the mammalian target of rapamycin (mTOR) was identified as the rapamycin target in mammals by David M. Sabatini and Solomon H. Snyder (Johns Hopkins University)[11] and Stuart L. Schreiber (Harvard University).[1]
Function
mTOR integrates the input from upstream pathways, including insulin, growth factors (such as IGF-1 and IGF-2), and amino acids.[3] mTOR also senses cellular nutrient, oxygen, and energy levels.[12] The mTOR pathway is dysregulated in human diseases, such as diabetes, obesity, depression, and certain cancers.[4] Rapamycin is a bacterial product that can inhibit mTOR by associating with its intracellular receptor FKBP12.[13][14] The FKBP12-rapamycin complex binds directly to the FKBP12-Rapamycin Binding (FRB) domain of mTOR, inhibiting its activity.[14]
mTOR stands for mammalian Target Of Rapamycin and was named based on the precedent that TOR was first discovered via genetic and molecular studies of rapamycin-resistant mutants of Saccharomyces cerevisiae that identified FKBP12, Tor1, and Tor2 as the targets of rapamycin and provided robust support that the FKBP12-rapamycin complex binds to and inhibits the cellular functions of Tor1 and Tor2.
Complexes
mTOR is the catalytic subunit of two molecular complexes: mTORC1 and mTORC2.[15]
mTORC1
mTOR Complex 1 (mTORC1) is composed of mTOR, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified partners PRAS40 and DEPTOR.[16][17] This complex is characterized by the classic features of mTOR by functioning as a nutrient/energy/redox sensor and controlling protein synthesis.[3][16] The activity of this complex is stimulated by insulin, growth factors, serum, phosphatidic acid, amino acids (particularly leucine), and oxidative stress.[16][18]
mTORC2
mTOR Complex 2 (mTORC2) is composed of mTOR, rapamycin-insensitive companion of mTOR (RICTOR), GβL, and mammalian stress-activated protein kinase interacting protein 1 (mSIN1).[19][20] mTORC2 has been shown to function as an important regulator of the cytoskeleton through its stimulation of F-actin stress fibers, paxillin, RhoA, Rac1, Cdc42, and protein kinase C α (PKCα).[20] mTORC2 also appears to possess the activity of a previously elusive protein known as "PDK2". mTORC2 phosphorylates the serine/threonine protein kinase Akt/PKB at a serine residue S473 . Phosphorylation of the serine stimulates Akt phosphorylation at a threonine T308 residue by PDK1 and leads to full Akt activation;[21][22] curcumin inhibits both by preventing phosphorylation of the serine.[4]
Rapamycin action on mTORC1 and mTORC2
Rapamycin inhibits mTORC1, and this appears to provide most of the beneficial effects of the drug (including life-lengthening in animal studies). Rapamycin also acts on mTORC2. Disruption of mTORC2 produces the diabetic-like symptoms of decreased glucose tolerance and insensitivity to insulin also associated with rapamycin.[23]
Physiological significance (KO phenotypes)
The mTORC2 signaling pathway is less clearly defined than the mTORC1 signaling pathway. Therefore, performing knockout experiments is a good way to shed light on more specific molecules and their roles in this pathway. Protein function inhibition using knockdowns and knockouts were found to produce the following phenotypes:
- NIP7: knockdown reduced mTORC2 activity which is indicated by decreased phosphorylation of mTORC2 substrates.[24]
- RICTOR: overexpression leads to metastasis and knockdown inhibits growth factor-induced PKC-phosphorylation.[25]
- mTOR: inhibition of mTORC1 and mTORC2 by PP242 [2-(4-Amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol] leads to autophagy or apoptosis; inhibition of mTORC2 alone by PP242 prevents phosphorylation of Ser-473 site on AKT and arrests the cells in G1 phase of the cell cycle.[26]
- PDK1: knockout is lethal; hypomorphic allele results in smaller organ volume and organism size, but normal AKT activation.[27]
- AKT: knockout mice experience spontaneous apoptosis (AKT1), severe diabetes (AKT2), small brains (AKT3), and growth deficiency (AKT1/AKT2) [28]
- TOR1, the S. cerevisiae orthologue of mTORC1, is a regulator of both carbon and nitrogen metabolism; TOR1 KO strains regulate response to nitrogen as well as carbon availability, indicating that it is a key nutritional transducer in yeast.[29][30]
Clinical significance
Aging
![](http://upload.wikimedia.org/wikipedia/commons/thumb/5/5c/MTOR-pathway-v1.7.svg/300px-MTOR-pathway-v1.7.svg.png)
Decreased TOR activity has been found to extend aging in S. cerevisiae, C. elegans, and D. melanogaster.[31][32][33][34] The mTOR inhibitor rapamycin has been confirmed to increase lifespan in mice by independent groups at the Jackson Laboratory, University of Texas Health Science Center, and the University of Michigan.[35]
It is hypothesized that some dietary regimes, like caloric restriction and methionine restriction, cause lifespan extension by decreasing mTOR activity.[31][32] But infusion of leucine into the rat brain has been shown to decrease food intake and body weight via activation of the mTOR pathway.[36]
In a systems biology study by A. Kriete et al. 2010,[37] effects of mTOR inhibition on aging are modeled: According to the free radical theory of aging, reactive oxygen species cause damage of mitochondrial proteins and decrease of ATP production. Subsequently, via ATP sensitive AMPK, the mTOR pathway is inhibited and ATP consuming protein synthesis is downregulated, since mTORC1 initiates a phosphorylation cascade activating the ribosome.[7] Hence, the proportion of damaged proteins is enhanced. Moreover, disruption of mTORC1 directly inhibits mitochondrial respiration.[38] These positive feedbacks on the aging process are counteracted by protective mechanisms: Decreased mTOR activity (among other factors) upregulates glycolysis[38] and removal of dysfunctional cellular components via autophagy.[37]
Alzheimer’s disease
mTOR signaling intersects with Alzheimer’s disease (AD) pathology in several aspects, suggesting its potential role as a contributor to disease progression. In general, findings demonstrate mTOR signaling hyperactivity in AD brains. For example, postmortem studies of human AD brain reveal dysregulation in PTEN, Akt, S6K, and mTOR.[39][40][41] mTOR signaling appears to be closely related to the presence of soluble amyloid beta (Aβ) and tau proteins, which aggregate and form two hallmarks of the disease, Aβ plaques and neurofibrillary tangles, respectively.[42] In vitro studies have shown Aβ to be an activator of the PI3K/AKT pathway, which in turn activates mTOR.[43] Additionally, applying Aβ to N2K cells increases the expression of p70S6K, a downstream target of mTOR known to have higher expression in neurons that eventually develop neurofibrillary tangles.[44][45] Chinese hamster ovary cells transfected with the 7PA2 familial AD mutation also exhibit increased mTOR activity compared to controls, and the hyperactivity is blocked using a gamma-secretase inhibitor.[46][47] These in vitro studies suggest that increasing Aβ concentrations increases mTOR signaling; however, significantly large, cytotoxic Aβ concentrations are thought to decrease mTOR signaling.[48]
Consistent with data observed in vitro, mTOR activity and activated p70S6K have been shown to be significantly increased in the cortex and hippocampus of animal models of AD compared to controls.[47][49] Pharmacologic or genetic removal of the Aβ in animal models of AD eliminates the disruption in normal mTOR activity, pointing to the direct involvement of Aβ in mTOR signaling.[49] Additionally, by injecting Aβ oligomers into the hippocampi of normal mice, mTOR hyperactivity is observed.[49] Cognitive impairments characteristic of AD appear to be mediated by the phosphorylation of PRAS-40, which detaches from and allows for the mTOR hyperactivity when it is phosphorylated; inhibiting PRAS-40 phosphorylation prevents Aβ-induced mTOR hyperactivity.[49][50][51] Given these findings, the mTOR signaling pathway appears to be one mechanism of Aβ-induced toxicity in AD.
The hyperphosphorylation of tau proteins into neurofibrillary tangles is one hallmark of AD. p70S6K activation has been shown to promote tangle formation as well as mTOR hyperactivity through increased phosphorylation and reduced dephosphorylation.[44][52][53][54] It has also been proposed that mTOR contributes to tau pathology by increasing the translation of tau and other proteins.[55]
Synaptic plasticity is a key contributor to learning and memory, two processes that are severely impaired in AD patients. Translational control, or the maintenance of protein homeostasis, has been shown to be essential for neural plasticity and is regulated by mTOR.[47][56][57][58][59] Both protein over- and under-production via mTOR activity seem to contribute to impaired learning and memory. Furthermore, given that deficits resulting from mTOR overactivity can be alleviated through treatment with rapamycin, it is possible that mTOR plays an important role in affecting cognitive functioning through synaptic plasticity.[43][60] Further evidence for mTOR activity in neurodegeneration comes from recent findings demonstrating that eIF2α-P, an upstream target of the mTOR pathway, mediates cell death in prion diseases through sustained translational inhibition.[61]
Some evidence points to mTOR’s role in reduced Aβ clearance as well. mTOR is a negative regulator of autophagy;[62] therefore, hyperactivity in mTOR signaling should reduce Aβ clearance in the AD brain. Several groups have proposed that disruptions in autophagy may be a potential source of pathogenesis in protein misfolding diseases, including AD.[63][64][65][66][67][68] Studies using mouse models of Huntington’s disease demonstrate that treatment with rapamycin facilitates the clearance of huntingtin aggregates.[69][70] Perhaps the same treatment may be useful in clearing Aβ deposits as well.
mTOR inhibitors as therapies
mTOR inhibitors, e.g. rapamycin, are already used to prevent transplant rejection. Rapamycin is also related to the therapy of glycogen storage disease (GSD). Some articles reported that rapamycin can inhibit mTORC1 so that the phosphorylation of GS(glycogen synthase) can be increased in skeletal muscle. This discovery represents a potential novel therapeutic approach for glycogen storage diseases that involve glycogen accumulation in muscle. Various natural compounds, including epigallocatechin gallate (EGCG), caffeine, curcumin, and resveratrol, have also been reported to inhibit mTOR when applied to isolated cells in culture;[4][71] however, there is as yet no evidence that these substances inhibit mTOR when taken as dietary supplements.
Some (e.g. temsirolimus, everolimus) are beginning to be used in the treatment of cancer.[72][73] mTOR inhibitors may also be useful for treating several age-associated diseases.[74] Ridaforolimus is another mTOR inhibitor, currently in clinical development.
Interactions
Mammalian target of rapamycin has been shown to interact with:[75]
- ABL1,[76]
- AKT1,[77][78][79]
- CLIP1,[80]
- EIF3F[81]
- EIF4EBP1,[82][83][84][85][86][87][88][89]
- FKBP1A,[90][91][92][93][94][95]
- GPHN,[96]
- KIAA1303,[82][83][84][85][90][91][97][98][99][100][101][102][103][104][105][106][107][108][109][110]
- PRKCD,[111]
- RHEB,[86][112][113][114]
- RICTOR,[90][91][98][100][107][109][110]
- RPS6KB1,[83][85][86][87][88][105][109][115][116][117][118][119][120][120][121][122]
- STAT1,[123]
- STAT3,[124][125] and
- UBQLN1.[126]
See also
References
- ^ a b Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL (1994). "A mammalian protein targeted by G1-arresting rapamycin-receptor complex". Nature. 369 (6483): 756–8. doi:10.1038/369756a0. PMID 8008069.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid8008069" was defined multiple times with different content (see the help page). - ^ Moore PA, Rosen CA, Carter KC (1996). "Assignment of the human FKBP12-rapamycin-associated protein (FARP) gene to chromosome 1p36 by fluorescence in situ hybridization". Genomics. 33 (2): 331–2. doi:10.1006/geno.1996.0206. PMID 8660990.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b c Hay N, Sonenberg N (2004). "Upstream and downstream of mTOR". Genes Dev. 18 (16): 1926–45. doi:10.1101/gad.1212704. PMID 15314020.
- ^ a b c d Beevers C, Li F, Liu L, Huang S (2006). "Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells". Int J Cancer. 119 (4): 757–64. doi:10.1002/ijc.21932. PMID 16550606.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Vézina C, Kudelski A, Sehgal SN (1975). "Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle". J. Antibiot. 28 (10): 721–6. doi:10.7164/antibiotics.28.721. PMID 1102508.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Dobashi Y, Watanabe Y, Miwa C, Suzuki S, Koyama S (2011). "Mammalian target of rapamycin: a central node of complex signaling cascades". Int J Clin Exp Pathol. 4 (5): 476–95. PMC 3127069. PMID 21738819.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Magnuson B, Ekim B, Fingar DC (2012). "Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks". Biochem. J. 441 (1): 1–21. doi:10.1042/BJ20110892. PMID 22168436.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Abraham RT, Wiederrecht GJ (1996). "Immunopharmacology of rapamycin". Annu. Rev. Immunol. 14: 483–510. doi:10.1146/annurev.immunol.14.1.483. PMID 8717522.
- ^ Heitman J, Movva NR, Hall MN (1991). "Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast". Science. 253 (5022): 905–9. doi:10.1126/science.1715094. PMID 1715094.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Foster KG, Fingar DC (2010). "Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony". J. Biol. Chem. 285 (19): 14071–7. doi:10.1074/jbc.R109.094003. PMC 2863215. PMID 20231296.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: unflagged free DOI (link) - ^ Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH (1994). "RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs". Cell. 78 (1): 35–43. doi:10.1016/0092-8674(94)90570-3. PMID 7518356.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Tokunaga C, Yoshino K, Yonezawa K (2004). "mTOR integrates amino acid- and energy-sensing pathways". Biochem Biophys Res Commun. 313 (2): 443–6. doi:10.1016/j.bbrc.2003.07.019. PMID 14684182.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Huang S, Houghton P (2001). "Mechanisms of resistance to rapamycins". Drug Resist Updat. 4 (6): 378–91. doi:10.1054/drup.2002.0227. PMID 12030785.
- ^ a b Huang S, Bjornsti M, Houghton P (2003). "Rapamycins: mechanism of action and cellular resistance". Cancer Biol Ther. 2 (3): 222–32. PMID 12878853.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Wullschleger S, Loewith R, Hall M (2006). "TOR signaling in growth and metabolism". Cell. 124 (3): 471–84. doi:10.1016/j.cell.2006.01.016. PMID 16469695.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b c Kim D, Sarbassov D, Ali S, King J, Latek R, Erdjument-Bromage H, Tempst P, Sabatini D (2002). "mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery". Cell. 110 (2): 163–75. doi:10.1016/S0092-8674(02)00808-5. PMID 12150925.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Kim D, Sarbassov D, Ali S, Latek R, Guntur K, Erdjument-Bromage H, Tempst P, Sabatini D (2003). "GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR". Mol Cell. 11 (4): 895–904. doi:10.1016/S1097-2765(03)00114-X. PMID 12718876.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J (2001). "Phosphatidic acid-mediated mitogenic activation of mTOR signaling". Science. 294 (5548): 1942–5. doi:10.1126/science.1066015. PMID 11729323.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Frias M, Thoreen C, Jaffe J, Schroder W, Sculley T, Carr S, Sabatini D (2006). "mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s". Curr Biol. 16 (18): 1865–70. doi:10.1016/j.cub.2006.08.001. PMID 16919458.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Sarbassov D, Ali S, Kim D, Guertin D, Latek R, Erdjument-Bromage H, Tempst P, Sabatini D (2004). "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton". Curr Biol. 14 (14): 1296–302. doi:10.1016/j.cub.2004.06.054. PMID 15268862.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Sarbassov D, Guertin D, Ali S, Sabatini D (2005). "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex". Science. 307 (5712): 1098–101. doi:10.1126/science.1106148. PMID 15718470.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Stephens L, Anderson K, Stokoe D, Erdjument-Bromage H, Painter G, Holmes A, Gaffney P, Reese C, McCormick F, Tempst P, Coadwell J, Hawkins P (1998). "Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B". Science. 279 (5351): 710–4. doi:10.1126/science.279.5351.710. PMID 9445477.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS, Guertin DA, Sabatini DM, Baur JA (2012). "Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity". Science. 335 (6076): 1638–43. doi:10.1126/science.1215135. PMC 3324089. PMID 22461615.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Zinzalla V, Stracka D, Oppliger W, Hall MN (2011). "Activation of mTORC2 by association with the ribosome". Cell. 144 (5): 757–68. doi:10.1016/j.cell.2011.02.014. PMID 21376236.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Zhang F, Zhang X, Li M, Chen P, Zhang B, Guo H, Cao W, Wei X, Cao X, Hao X, Zhang N (2010). "mTOR complex component Rictor interacts with PKCzeta and regulates cancer cell metastasis". Cancer Res. 70 (22): 9360–70. doi:10.1158/0008-5472.CAN-10-0207. PMID 20978191.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Feldman ME, Apsel B, Uotila A, Loewith R, Knight ZA, Ruggero D, Shokat KM (2009). Hunter, Tony (ed.). "Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2". PLoS Biol. 7 (2): e38. doi:10.1371/journal.pbio.1000038. PMC 2637922. PMID 19209957.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Lawlor MA, Mora A, Ashby PR, Williams MR, Murray-Tait V, Malone L, Prescott AR, Lucocq JM, Alessi DR (2002). "Essential role of PDK1 in regulating cell size and development in mice". EMBO J. 21 (14): 3728–38. doi:10.1093/emboj/cdf387. PMC 126129. PMID 12110585.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Yang ZZ, Tschopp O, Baudry A, Dümmler B, Hynx D, Hemmings BA (2004). "Physiological functions of protein kinase B/Akt". Biochem. Soc. Trans. 32 (Pt 2): 350–4. doi:10.1042/BST0320350. PMID 15046607.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Crespo, J and Hall, M (2002). "Elucidating TOR signaling and rapamycin action: lessons from Saccharomyces cerevisiae". Microbiol Mol Biol Rev. 66 (4): 579–591. PMC 134654. PMID 12456783.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Peter, GJ, During, L, Ahmed, A (2006). "Carbon catabolite repression regulates amino acid permeases in Saccharomyces cerevisiae via the TOR signaling pathway". J Biol Chem. 28 (9): 5546–5552. doi:10.1074/jbc.M513842200. PMID 16407266.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Powers RW, Kaeberlein M, Caldwell SD, Kennedy BK, Fields S (2006). "Extension of chronological life span in yeast by decreased TOR pathway signaling". Genes Dev. 20 (2): 174–84. doi:10.1101/gad.1381406. PMC 1356109. PMID 16418483.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Kaeberlein M, Powers RW, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK (2005). "Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients". Science. 310 (5751): 1193–6. doi:10.1126/science.1115535. PMID 16293764.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Jia K, Chen D, Riddle DL (2004). "The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span". Development. 131 (16): 3897–906. doi:10.1242/dev.01255. PMID 15253933.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S (2004). "Regulation of Lifespan in Drosophila by Modulation of Genes in the TOR Signaling Pathway". Curr. Biol. 14 (10): 885–90. doi:10.1016/j.cub.2004.03.059. PMC 2754830. PMID 15186745.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009). "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice". Nature. 460 (7253): 392–5. doi:10.1038/nature08221. PMC 2786175. PMID 19587680.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC, Seeley RJ (2006). "Hypothalamic mTOR signaling regulates food intake". Science. 312 (5775): 927–930. doi:10.1126/science.1124147. PMID 16690869.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Kriete A, Bosl WJ, Booker G (2010). "Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses". PLoS Computational Biology. 6 (6): e1000820. doi:10.1371/journal.pcbi.1000820. PMC 2887462.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Schieke SM, Phillips D, McCoy Jr. JP, Aponte AM, Shen RF, Balaban RS, Finkel T (2006). "The Mammalian Target of Rapamycin (mTOR) Pathway Regulates Mitochondrial Oxygen Consumption and Oxidative Capacity". J. Biol. Chem. 281: 27643–27652. doi:10.1074/jbc.M603536200. PMID 16847060.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Rosner M, Hanneder M, Siegel N, Valli A, Fuchs C, Hengstschläger M. (2008). "The mTOR pathway and its role in human genetic diseases". Mutat. Res. 659 (3): 284–92. doi:10.1016/j.mrrev.2008.06.001. PMID 18598780.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Li X, Alafuzoff I, Soininen H, Winblad B, Pei JJ. (2005). "Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain". FEBS J. 272 (16): 4211–20. doi:10.1111/j.1742-4658.2005.04833.x. PMID 16098202.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Chano T, Okabe H, Hulette CM. (2007). "RB1CC1 insufficiency causes neuronal atrophy through mTOR signaling alteration and involved in the pathology of Alzheimer's diseases". Brain Res. 1168 (1168): 97–105. doi:10.1016/j.brainres.2007.06.075. PMID 17706618.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Selkoe DJ (2008). "Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior". Behav Brain Res. 192 (1): 106–13. doi:10.1016/j.bbr.2008.02.016. PMID 18359102.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ a b Oddo S (2012). "The role of mTOR signaling in Alzheimer disease". Front Biosci. 4 (4): 941–52. PMID 22202101.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ a b An WL, Cowburn RF, Li L, Braak H, Alafuzoff I, Iqbal K, Iqbal IG, Winblad B, Pei JJ. (2003). "Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease". Am J Pathol. 163 (2): 591–607. doi:10.1016/S0002-9440(10)63687-5. PMC 1868198. PMID 12875979.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Zhang F, Beharry ZM, Harris TE, Lilly MB, Smith CD, Mahajan S, Kraft AS. (2009). "PIM1 protein kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cells". Cancer Biol Ther. 8 (9): 846–53. PMID 19276681.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Koo EH, Squazzo SL. (1994). "Evidence that production and release of amyloid beta-protein involves the endocytic pathway". J Biol Chem. 269 (26): 17386–9. PMID 8021238.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ a b c Caccamo A, Majumder S, Richardson A, Strong R, Oddo S. (2010). "Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments". J Biol Chem. 285 (17): 13107–20. doi:10.1074/jbc.M110.100420. PMC 2857107. PMID 20178983.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Lafay-Chebassier C, Paccalin M, Page G, Barc-Pain S, Perault-Pochat MC, Gil R, Pradier L, Hugon J. (2005). "mTOR/p70S6k signalling alteration by Abeta exposure as well as in APP-PS1 transgenic models and in patients with Alzheimer's disease". J Neurochem. 94 (1): 215–25. doi:10.1111/j.1471-4159.2005.03187.x. PMID 15953364.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b c d Caccamo A, Maldonado MA, Majumder S, Medina DX, Holbein W, Magrí A, Oddo S. (2011). "Naturally secreted amyloid-beta increases mammalian target of rapamycin (mTOR) activity via a PRAS40-mediated mechanism". J Biol Chem. 286 (11): 8924–32. doi:10.1074/jbc.M110.180638. PMC 3058958. PMID 21266573.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Sancak Y, Thoreen CC, Peterson TR, Lindquist RA, Kang SA, Spooner E, Carr SA, Sabatini DM. (2007). "PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase". Mol Cell. 25 (6): 903–15. doi:10.1016/j.molcel.2007.03.003. PMID 17386266.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Wang L, Harris TE, Roth RA, Lawrence JC Jr. (2007). "PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding". J. Biol Chem. 282 (27): 20036–44. doi:10.1074/jbc.M702376200. PMID 17510057.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Pei JJ, Hugon J. (2008). "mTOR-dependent signalling in Alzheimer's disease". J Cell Mol Med. 12 (6B): 2525–32. doi:10.1111/j.1582-4934.2008.00509.x. PMID 19210753.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Meske V, Albert F, Ohm TG. (2008). "Coupling of mammalian target of rapamycin with phosphoinositide 3-kinase signaling pathway regulates protein phosphatase 2A- and glycogen synthase kinase-3 -dependent phosphorylation of Tau". J Biol Chem. 293 (1): 100–9. doi:10.1074/jbc.M704292200. PMID 17971449.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Janssens V, Goris J. (2001). "Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling". Biochem J. 353 (Pt 3): 417–39. PMC 1221586. PMID 11171037.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Morita T, Sobue K. (2009). "Specification of neuronal polarity regulated by local translation of CRMP2 and Tau via the mTOR-p70S6K pathway". J Biol Chem. 284 (40): 27734–45. doi:10.1074/jbc.M109.008177. PMC 2785701. PMID 19648118.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: unflagged free DOI (link) - ^ Puighermanal E, Marsicano G, Busquets-Garcia A, Lutz B, Maldonado R, Ozaita A. (2009). "Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling". Nat Neurosci. 12 (9): 1152–8. doi:10.1038/nn.2369. PMID 19648913.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Tischmeyer W, Schicknick H, Kraus M, Seidenbecher CI, Staak S, Scheich H, Gundelfinger ED. (2003). "Rapamycin-sensitive signalling in long-term consolidation of auditory cortex-dependent memory". Eur J Neurosci. 18 (4): 942–50. PMID 12925020.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Hoeffer CA, Klann E. (2010). "mTOR signaling: at the crossroads of plasticity, memory and disease". Trends Neurosci. 33 (2): 67–75. doi:10.1016/j.tins.2009.11.003. PMID 19963289.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Kelleher RJ 3rd, Govindarajan A, Jung HY, Kang H, Tonegawa S. (2004). "Translational control by MAPK signaling in long-term synaptic plasticity and memory". Cell. 116 (3): 467–79. doi:10.1016/S0092-8674(04)00115-1. PMID 15016380.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link) - ^ Ehninger D, Han S, Shilyansky C, Zhou Y, Li W, Kwiatkowski DJ, Ramesh V, Silva AJ. (2008). "Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis". Nat Med. 14 (8): 843–8. doi:10.1038/nm1788. PMC 2664098. PMID 18568033.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Martin MG, Halliday M, Morgan J, Dinsdale D, Ortori CA, Barrett DA, Tsaytler P, Bertolotti A, Willis AE, Bushell M, Mallucci GR (2012). "Sustained translational repression by eIF2α-P mediates prion neurodegeneration". Nature. 485 (7399): 507–11. doi:10.1038/nature11058. PMC 3378208. PMID 22622579.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Díaz-Troya S, Pérez-Pérez ME, Florencio FJ, Crespo JL. (2008). "The role of TOR in autophagy regulation from yeast to plants and mammals". Autophagy. 4 (7): 851–65. PMID 18670193.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ McCray BA, Taylor JP. (2008). "The role of autophagy in age-related neurodegeneration". Neurosignals. 16 (1): 75–84. doi:10.1159/000109761. PMID 18097162.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Nedelsky NB, Todd PK, Taylor JP. (2008). "Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection". Biochim Biophys Acta. 1782 (12): 691–9. doi:10.1016/j.bbadis.2008.10.002. PMID 18930136.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ David C. Rubinsztein (2006). "The roles of intracellular protein-degradation pathways in neurodegeneration". Nature. 443 (7113): 780–786. doi:10.1038/nature05291. PMID 17051204.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Oddo S. (2008). "The ubiquitin-proteasome system in Alzheimer's disease". J Cell Mol Med. 12 (2): 363–73. doi:10.1111/j.1582-4934.2008.00276.x. PMID 18266959.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Li X, Li H, Li XJ. (2008). "Intracellular degradation of misfolded proteins in polyglutamine neurodegenerative diseases". Brain Res Rev. 59 (1): 245–52. doi:10.1016/j.brainresrev.2008.08.003. PMID 18773920.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Caccamo A, Majumder S, Deng JJ, Bai Y, Thornton FB, Oddo S. (2009). "Rapamycin rescues TDP-43 mislocalization and the associated low molecular mass neurofilament instability". J Biol Chem. 284 (40): 27416–24. doi:10.1074/jbc.M109.031278. PMC 2785671. PMID 19651785.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, Scaravilli F, Easton DF, Duden R, O'Kane CJ, Rubinsztein DC. (2004). "Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease". Nat. Genet. 36 (6): 585–95. doi:10.1038/ng1362. PMID 15146184.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Rami A. (2009). "Review: autophagy in neurodegeneration: firefighter and/or incendiarist?". Neuropathol Appl Neurobio. 35 (5): 449–61. doi:10.1111/j.1365-2990.2009.01034.x. PMID 19555462.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Zhou H, Luo Y, Huang S (2010). "Updates of mTOR inhibitors". Anticancer Agents Med Chem. 10 (7): 571–81. PMC 2980558. PMID 20812900.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Easton JB, Houghton PJ (2006). "mTOR and cancer therapy". Oncogene. 25 (48): 6436–46. doi:10.1038/sj.onc.1209886. PMID 17041628.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Faivre S, Kroemer G, Raymond E (2006). "Current development of mTOR inhibitors as anticancer agents". Nat Rev Drug Discov. 5 (8): 671–88. doi:10.1038/nrd2062. PMID 16883305.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Hasty P (2010). "Rapamycin: the cure for all that ails". J Mol Cell Biol. 2 (1): 17–9. doi:10.1093/jmcb/mjp033. PMID 19805415.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ "mTOR protein interactors". Human Protein Reference Database. Johns Hopkins University and the Institute of Bioinformatics. Retrieved 2010-12-06.
{{cite web}}
: Cite has empty unknown parameter:|coauthors=
(help) - ^ Kumar V, Sabatini D, Pandey P, Gingras AC, Majumder PK, Kumar M, Yuan ZM, Carmichael G, Weichselbaum R, Sonenberg N, Kufe D, Kharbanda S (2000). "Regulation of the rapamycin and FKBP-target 1/mammalian target of rapamycin and cap-dependent initiation of translation by the c-Abl protein-tyrosine kinase". J. Biol. Chem. 275 (15): 10779–87. doi:10.1074/jbc.275.15.10779. PMID 10753870.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005). "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex". Science. 307 (5712): 1098–101. doi:10.1126/science.1106148. PMID 15718470.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Sekulić A, Hudson CC, Homme JL, Yin P, Otterness DM, Karnitz LM, Abraham RT (2000). "A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells". Cancer Res. 60 (13): 3504–13. PMID 10910062.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Cheng SW, Fryer LG, Carling D, Shepherd PR (2004). "Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status". J. Biol. Chem. 279 (16): 15719–22. doi:10.1074/jbc.C300534200. PMID 14970221.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Choi JH, Bertram PG, Drenan R, Carvalho J, Zhou HH, Zheng XF (2002). "The FKBP12-rapamycin-associated protein (FRAP) is a CLIP-170 kinase". EMBO Rep. 3 (10): 988–94. doi:10.1093/embo-reports/kvf197. PMC 1307618. PMID 12231510.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Harris TE, Chi A, Shabanowitz J, Hunt DF, Rhoads RE, Lawrence JC (2006). "mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin". EMBO J. 25 (8): 1659–68. doi:10.1038/sj.emboj.7601047. PMC 1440840. PMID 16541103.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Schalm SS, Fingar DC, Sabatini DM, Blenis J (2003). "TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function". Curr. Biol. 13 (10): 797–806. doi:10.1016/S0960-9822(03)00329-4. PMID 12747827.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b c Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K (2002). "Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action". Cell. 110 (2): 177–89. doi:10.1016/S0092-8674(02)00833-4. PMID 12150926.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Wang L, Rhodes CJ, Lawrence JC (2006). "Activation of mammalian target of rapamycin (mTOR) by insulin is associated with stimulation of 4EBP1 binding to dimeric mTOR complex 1". J. Biol. Chem. 281 (34): 24293–303. doi:10.1074/jbc.M603566200. PMID 16798736.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b c Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2002). "mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery". Cell. 110 (2): 163–75. doi:10.1016/S0092-8674(02)00808-5. PMID 12150925.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b c Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J (2005). "Rheb binds and regulates the mTOR kinase". Curr. Biol. 15 (8): 702–13. doi:10.1016/j.cub.2005.02.053. PMID 15854902.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Takahashi T, Hara K, Inoue H, Kawa Y, Tokunaga C, Hidayat S, Yoshino K, Kuroda Y, Yonezawa K (2000). "Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro". Genes Cells. 5 (9): 765–75. doi:10.1046/j.1365-2443.2000.00365.x. PMID 10971657.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Burnett PE, Barrow RK, Cohen NA, Snyder SH, Sabatini DM (1998). "RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1". Proc. Natl. Acad. Sci. U.S.A. 95 (4): 1432–7. doi:10.1073/pnas.95.4.1432. PMC 19032. PMID 9465032.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Wang X, Beugnet A, Murakami M, Yamanaka S, Proud CG (2005). "Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins". Mol. Cell. Biol. 25 (7): 2558–72. doi:10.1128/MCB.25.7.2558-2572.2005. PMC 1061630. PMID 15767663.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b c Jacinto E, Loewith R, Schmidt A, Lin S, Rüegg MA, Hall A, Hall MN (2004). "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive". Nat. Cell Biol. 6 (11): 1122–8. doi:10.1038/ncb1183. PMID 15467718.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b c Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2004). "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton". Curr. Biol. 14 (14): 1296–302. doi:10.1016/j.cub.2004.06.054. PMID 15268862.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Choi J, Chen J, Schreiber SL, Clardy J (1996). "Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP". Science. 273 (5272): 239–42. doi:10.1126/science.273.5272.239. PMID 8662507.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Luker KE, Smith MC, Luker GD, Gammon ST, Piwnica-Worms H, Piwnica-Worms D (2004). "Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12288–93. doi:10.1073/pnas.0404041101. PMC 514471. PMID 15284440.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Banaszynski LA, Liu CW, Wandless TJ (2005). "Characterization of the FKBP.rapamycin.FRB ternary complex". J. Am. Chem. Soc. 127 (13): 4715–21. doi:10.1021/ja043277y. PMID 15796538.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Sabers CJ, Martin MM, Brunn GJ, Williams JM, Dumont FJ, Wiederrecht G, Abraham RT (1995). "Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells". J. Biol. Chem. 270 (2): 815–22. doi:10.1074/jbc.270.2.815. PMID 7822316.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Sabatini DM, Barrow RK, Blackshaw S, Burnett PE, Lai MM, Field ME, Bahr BA, Kirsch J, Betz H, Snyder SH (1999). "Interaction of RAFT1 with gephyrin required for rapamycin-sensitive signaling". Science. 284 (5417): 1161–4. doi:10.1126/science.284.5417.1161. PMID 10325225.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Ha SH, Kim DH, Kim IS, Kim JH, Lee MN, Lee HJ, Kim JH, Jang SK, Suh PG, Ryu SH (2006). "PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals". Cell. Signal. 18 (12): 2283–91. doi:10.1016/j.cellsig.2006.05.021. PMID 16837165.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Frias MA, Thoreen CC, Jaffe JD, Schroder W, Sculley T, Carr SA, Sabatini DM (2006). "mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s". Curr. Biol. 16 (18): 1865–70. doi:10.1016/j.cub.2006.08.001. PMID 16919458.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Buerger C, DeVries B, Stambolic V (2006). "Localization of Rheb to the endomembrane is critical for its signaling function". Biochem. Biophys. Res. Commun. 344 (3): 869–80. doi:10.1016/j.bbrc.2006.03.220. PMID 16631613.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Jacinto E, Facchinetti V, Liu D, Soto N, Wei S, Jung SY, Huang Q, Qin J, Su B (2006). "SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity". Cell. 127 (1): 125–37. doi:10.1016/j.cell.2006.08.033. PMID 16962653.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ McMahon LP, Yue W, Santen RJ, Lawrence JC (2005). "Farnesylthiosalicylic acid inhibits mammalian target of rapamycin (mTOR) activity both in cells and in vitro by promoting dissociation of the mTOR-raptor complex". Mol. Endocrinol. 19 (1): 175–83. doi:10.1210/me.2004-0305. PMID 15459249.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Oshiro N, Yoshino K, Hidayat S, Tokunaga C, Hara K, Eguchi S, Avruch J, Yonezawa K (2004). "Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function". Genes Cells. 9 (4): 359–66. doi:10.1111/j.1356-9597.2004.00727.x. PMID 15066126.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Kawai S, Enzan H, Hayashi Y, Jin YL, Guo LM, Miyazaki E, Toi M, Kuroda N, Hiroi M, Saibara T, Nakayama H (2003). "Vinculin: a novel marker for quiescent and activated hepatic stellate cells in human and rat livers". Virchows Arch. 443 (1): 78–86. doi:10.1007/s00428-003-0804-4. PMID 12719976.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Choi KM, McMahon LP, Lawrence JC (2003). "Two motifs in the translational repressor PHAS-I required for efficient phosphorylation by mammalian target of rapamycin and for recognition by raptor". J. Biol. Chem. 278 (22): 19667–73. doi:10.1074/jbc.M301142200. PMID 12665511.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, Hara K, Tanaka N, Avruch J, Yonezawa K (2003). "The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif". J. Biol. Chem. 278 (18): 15461–4. doi:10.1074/jbc.C200665200. PMID 12604610.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Schieke SM, Phillips D, McCoy JP, Aponte AM, Shen RF, Balaban RS, Finkel T (2006). "The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity". J. Biol. Chem. 281 (37): 27643–52. doi:10.1074/jbc.M603536200. PMID 16847060.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM (2006). "Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB". Mol. Cell. 22 (2): 159–68. doi:10.1016/j.molcel.2006.03.029. PMID 16603397.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Tzatsos A, Kandror KV (2006). "Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation". Mol. Cell. Biol. 26 (1): 63–76. doi:10.1128/MCB.26.1.63-76.2006. PMC 1317643. PMID 16354680.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ a b c Sarbassov DD, Sabatini DM (2005). "Redox regulation of the nutrient-sensitive raptor-mTOR pathway and complex". J. Biol. Chem. 280 (47): 39505–9. doi:10.1074/jbc.M506096200. PMID 16183647.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: unflagged free DOI (link) - ^ a b Yang Q, Inoki K, Ikenoue T, Guan KL (2006). "Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity". Genes Dev. 20 (20): 2820–32. doi:10.1101/gad.1461206. PMC 1619946. PMID 17043309.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Kumar V, Pandey P, Sabatini D, Kumar M, Majumder PK, Bharti A, Carmichael G, Kufe D, Kharbanda S (2000). "Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation". EMBO J. 19 (5): 1087–97. doi:10.1093/emboj/19.5.1087. PMC 305647. PMID 10698949.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Long X, Ortiz-Vega S, Lin Y, Avruch J (2005). "Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency". J. Biol. Chem. 280 (25): 23433–6. doi:10.1074/jbc.C500169200. PMID 15878852.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Smith EM, Finn SG, Tee AR, Browne GJ, Proud CG (2005). "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 (19): 18717–27. doi:10.1074/jbc.M414499200. PMID 15772076.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Bernardi R, Guernah I, Jin D, Grisendi S, Alimonti A, Teruya-Feldstein J, Cordon-Cardo C, Simon MC, Rafii S, Pandolfi PP (2006). "PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR". Nature. 442 (7104): 779–85. doi:10.1038/nature05029. PMID 16915281.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Saitoh M, Pullen N, Brennan P, Cantrell D, Dennis PB, Thomas G (2002). "Regulation of an activated S6 kinase 1 variant reveals a novel mammalian target of rapamycin phosphorylation site". J. Biol. Chem. 277 (22): 20104–12. doi:10.1074/jbc.M201745200. PMID 11914378.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Chiang GG, Abraham RT (2005). "Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase". J. Biol. Chem. 280 (27): 25485–90. doi:10.1074/jbc.M501707200. PMID 15899889.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: unflagged free DOI (link) - ^ Holz MK, Blenis J (2005). "Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase". J. Biol. Chem. 280 (28): 26089–93. doi:10.1074/jbc.M504045200. PMID 15905173.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: unflagged free DOI (link) - ^ Isotani S, Hara K, Tokunaga C, Inoue H, Avruch J, Yonezawa K (1999). "Immunopurified mammalian target of rapamycin phosphorylates and activates p70 S6 kinase alpha in vitro". J. Biol. Chem. 274 (48): 34493–8. doi:10.1074/jbc.274.48.34493. PMID 10567431.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Toral-Barza L, Zhang WG, Lamison C, Larocque J, Gibbons J, Yu K (2005). "Characterization of the cloned full-length and a truncated human target of rapamycin: activity, specificity, and enzyme inhibition as studied by a high capacity assay". Biochem. Biophys. Res. Commun. 332 (1): 304–10. doi:10.1016/j.bbrc.2005.04.117. PMID 15896331.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Ali SM, Sabatini DM (2005). "Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif site". J. Biol. Chem. 280 (20): 19445–8. doi:10.1074/jbc.C500125200. PMID 15809305.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: unflagged free DOI (link) - ^ Edinger AL, Linardic CM, Chiang GG, Thompson CB, Abraham RT (2003). "Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells". Cancer Res. 63 (23): 8451–60. PMID 14679009.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Leone M, Crowell KJ, Chen J, Jung D, Chiang GG, Sareth S, Abraham RT, Pellecchia M (2006). "The FRB domain of mTOR: NMR solution structure and inhibitor design". Biochemistry. 45 (34): 10294–302. doi:10.1021/bi060976. PMID 16922504.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Kristof AS, Marks-Konczalik J, Billings E, Moss J (2003). "Stimulation of signal transducer and activator of transcription-1 (STAT1)-dependent gene transcription by lipopolysaccharide and interferon-gamma is regulated by mammalian target of rapamycin". J. Biol. Chem. 278 (36): 33637–44. doi:10.1074/jbc.M301053200. PMID 12807916.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Yokogami K, Wakisaka S, Avruch J, Reeves SA (2000). "Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR". Curr. Biol. 10 (1): 47–50. doi:10.1016/S0960-9822(99)00268-7. PMID 10660304.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Kusaba H, Ghosh P, Derin R, Buchholz M, Sasaki C, Madara K, Longo DL (2005). "Interleukin-12-induced interferon-gamma production by human peripheral blood T cells is regulated by mammalian target of rapamycin (mTOR)". J. Biol. Chem. 280 (2): 1037–43. doi:10.1074/jbc.M405204200. PMID 15522880.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Wu S, Mikhailov A, Kallo-Hosein H, Hara K, Yonezawa K, Avruch J (2002). "Characterization of ubiquilin 1, an mTOR-interacting protein". Biochim. Biophys. Acta. 1542 (1–3): 41–56. doi:10.1016/S0167-4889(01)00164-1. PMID 11853878.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link)
Further reading
- Huang S, Houghton PJ (2002). "Mechanisms of resistance to rapamycins". Drug Resist. Updat. 4 (6): 378–91. doi:10.1054/drup.2002.0227. PMID 12030785.
- Harris TE, Lawrence JC (2004). "TOR signaling". Sci. STKE. 2003 (212): re15. doi:10.1126/stke.2122003re15. PMID 14668532.
- Easton JB, Houghton PJ (2005). "Therapeutic potential of target of rapamycin inhibitors". Expert Opin. Ther. Targets. 8 (6): 551–64. doi:10.1517/14728222.8.6.551. PMID 15584862.
- Deldicque L, Theisen D, Francaux M (2005). "Regulation of mTOR by amino acids and resistance exercise in skeletal muscle". Eur. J. Appl. Physiol. 94 (1–2): 1–10. doi:10.1007/s00421-004-1255-6. PMID 15702344.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - Weimbs T (2007). "Regulation of mTOR by polycystin-1: is polycystic kidney disease a case of futile repair?". Cell Cycle. 5 (21): 2425–9. doi:10.4161/cc.5.21.3408. PMID 17102641.
- Sun SY, Fu H, Khuri FR (2007). "Targeting mTOR signaling for lung cancer therapy". Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 1 (2): 109–11. PMID 17409838.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - Abraham RT, Gibbons JJ (2007). "The mammalian target of rapamycin signaling pathway: twists and turns in the road to cancer therapy". Clin. Cancer Res. 13 (11): 3109–14. doi:10.1158/1078-0432.CCR-06-2798. PMID 17545512.
- Quaresma AJ, Sievert R, Nickerson JA (2013). "Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway". Mol. Biol. Cell. April (8): 1208–21. doi:10.1091/mbc.E12-06-0450. PMC 3623641. PMID 23427269.
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: CS1 maint: multiple names: authors list (link)
External links
- http://www.TargetmTOR.com
- mTOR+protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)