PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33174028-13 2020 Furthermore, depleting expression of RAGE or mTORC2 protein components (rapamycin-insensitive companion of mTOR) by small interfering RNA was found to reduce the cell viability, migration and angiogenesis of S100A8/9-treated HUVECs. Sirolimus 72-81 CREB regulated transcription coactivator 2 Mus musculus 45-51 33013932-3 2020 Our results show that RLR stimulation increased the phosphorylation of the mTOR complex (mTORC) 1 and mTORC2 downstream targets p70S6 kinase and Akt, respectively, and this process was prevented by the mTORC1 inhibitor rapamycin as well as the dual mTORC1/C2 kinase inhibitor AZD8055 in both DC subtypes. Sirolimus 219-228 CREB regulated transcription coactivator 2 Mus musculus 102-108 33319180-5 2020 Rapamycin inhibited mTORC1 and PTEN, but augmented mTORC2 with restoration of miRNA-302a under diabetic conditions. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 51-57 33319180-7 2020 We conclude that rapamycin attenuates reperfusion injury in diabetic heart through inhibition of PTEN and mTORC1 with restoration of miR-302a-mTORC2 signaling. Sirolimus 17-26 CREB regulated transcription coactivator 2 Mus musculus 142-148 31738412-10 2020 In addition, RAPA restored AKT phosphorylation (target of mTORC2), but suppressed S6 phosphorylation (target of mTORC1) following I/R injury. Sirolimus 13-17 CREB regulated transcription coactivator 2 Mus musculus 58-64 32905798-5 2020 HFSC fate reversibility and glutamine metabolism are regulated by the mammalian target of rapamycin complex 2 (mTORC2)-Akt signaling axis within the niche. Sirolimus 90-99 CREB regulated transcription coactivator 2 Mus musculus 111-117 32647003-5 2020 HEM1 loss also blocked mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, T cell proliferation, and selected effector functions, leading to immunodeficiency. Sirolimus 45-54 CREB regulated transcription coactivator 2 Mus musculus 66-72 32923403-5 2020 Application of mTORC1/2 inhibitors (AZD8055, WYE-125132, MTI-31, and rapamycin) or genetic mTORC-depletion all reduced TF expression, which appeared to be differentially mediated depending on cellular context. Sirolimus 69-78 CREB regulated transcription coactivator 2 Mus musculus 15-23 32720643-1 2020 Inhibition of mTOR (mechanistic Target Of Rapamycin) signaling by rapamycin promotes healthspan and longevity more strongly in females than males, perhaps because inhibition of hepatic mTORC2 (mTOR Complex 2) specifically reduces the lifespan of males. Sirolimus 66-75 CREB regulated transcription coactivator 2 Mus musculus 185-191 32666017-4 2020 One key complex that regulates beta-catenin activity is the mammalian target of rapamycin complex 2 (mTORc2). Sirolimus 80-89 CREB regulated transcription coactivator 2 Mus musculus 101-107 33183203-4 2020 An innovative strategy involves the vitamin nicotinamide and the pathways associated with the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), the mechanistic target of rapamycin (mTOR), mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), AMP activated protein kinase (AMPK), and clock genes. Sirolimus 210-219 CREB regulated transcription coactivator 2 Mus musculus 269-275 31509054-3 2020 In this study we found that during integrin alphaIIbbeta3 outside-in signaling PI3Kbeta-dependent phosphorylation of Akt on Serine473 is mediated by the mammalian target of rapamycin complex 2 (mTORC2). Sirolimus 173-182 CREB regulated transcription coactivator 2 Mus musculus 194-200 32035060-3 2020 Mammalian target of rapamycin complex 2 (mTORC2) was identified to regulate cell metabolism, proliferation and survival. Sirolimus 20-29 CREB regulated transcription coactivator 2 Mus musculus 41-47 32023458-6 2020 MGO induces AKT activation through phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin 2 (mTORC2) and Hsp27 regulation. Sirolimus 92-101 CREB regulated transcription coactivator 2 Mus musculus 105-111 32046043-6 2020 Silencing of PARP2 inhibited the activity of AMP-activated kinase (AMPK) and the mammalian target of rapamycin complex 2 (mTORC2). Sirolimus 101-110 CREB regulated transcription coactivator 2 Mus musculus 122-128 31825077-3 2020 Placental mechanistic target of rapamycin Complex 2 (mTORC2) signaling is inhibited in IUGR and regulates the trafficking of key amino acid transporter (AAT) isoforms to the ST plasma membrane, however the molecular mechanisms are unknown. Sirolimus 32-41 CREB regulated transcription coactivator 2 Mus musculus 53-59 30794726-2 2020 However, the side effects associated with long-term rapamycin treatment, many of which are due to inhibition of a second mTOR complex, mTORC2, have seemed to preclude the routine use of rapamycin as a therapy for age-related diseases. Sirolimus 52-61 CREB regulated transcription coactivator 2 Mus musculus 135-141 30794726-2 2020 However, the side effects associated with long-term rapamycin treatment, many of which are due to inhibition of a second mTOR complex, mTORC2, have seemed to preclude the routine use of rapamycin as a therapy for age-related diseases. Sirolimus 186-195 CREB regulated transcription coactivator 2 Mus musculus 135-141 31771139-3 2019 Our studies have identified RICTOR, PRR5, and SIN1 subunits of the mammalian target of rapamycin complex 2 (mTORC2) as interacting partners with the tBRCT domain of BRCA1 leading to the disruption of the mTORC2 complex. Sirolimus 87-96 CREB regulated transcription coactivator 2 Mus musculus 108-114 32579497-3 2020 Alcohol via upstream kinases like mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCepsilon or vice versa in AUD. Sirolimus 54-63 CREB regulated transcription coactivator 2 Mus musculus 89-95 31699566-1 2020 The target of rapamycin complex 2 (TORC2) was discovered in 2002 in budding yeast. Sirolimus 14-23 CREB regulated transcription coactivator 2 Mus musculus 35-40 31493485-8 2019 This model shows that rapamycin has stronger effects on mTORC1 compared with mTORC2, simply due to its direct interaction with free mTOR and mTORC1, but not mTORC2, without the need to consider other components that might further stabilize mTORC2. Sirolimus 22-31 CREB regulated transcription coactivator 2 Mus musculus 77-83 31493485-9 2019 Based on our results, even when mTORC2 is less stable compared with mTORC1, it can be less inhibited by rapamycin. Sirolimus 104-113 CREB regulated transcription coactivator 2 Mus musculus 32-38 31712311-2 2019 Here we show that in the highly lethal brain tumor glioblastoma (GBM), mechanistic target of rapamycin complex 2 (mTORC2), a critical core component of the growth factor signaling system, couples acetyl-CoA production with nuclear translocation of histone-modifying enzymes including pyruvate dehydrogenase (PDH) and class IIa histone deacetylases (HDACs) to globally alter histone acetylation. Sirolimus 93-102 CREB regulated transcription coactivator 2 Mus musculus 114-120 31791403-1 2019 BACKGROUND: The mammalian target of rapamycin complex 2 (mTORC2), containing the essential protein rictor, regulates cellular metabolism and cytoskeletal organization by phosphorylating protein kinases, such as PKB/Akt, PKC, and SGK. Sirolimus 36-45 CREB regulated transcription coactivator 2 Mus musculus 57-63 31882658-6 2019 Inhibition of mTORC1 with Rapamycin elicited reciprocal activation of mTORC2, enhanced autophagy and recruited anti-apoptotic signals, conferring protection from calcification. Sirolimus 26-35 CREB regulated transcription coactivator 2 Mus musculus 70-76 31857853-2 2019 Many of the effects of SESTRINs are mediated by negative and positive regulation of mechanistic target of rapamycin kinase complexes 1 and 2 (mTORC1 and mTORC2), respectively, that are often deregulated in human cancers where they support cell growth, proliferation, and cell viability. Sirolimus 106-115 CREB regulated transcription coactivator 2 Mus musculus 153-159 31771139-3 2019 Our studies have identified RICTOR, PRR5, and SIN1 subunits of the mammalian target of rapamycin complex 2 (mTORC2) as interacting partners with the tBRCT domain of BRCA1 leading to the disruption of the mTORC2 complex. Sirolimus 87-96 CREB regulated transcription coactivator 2 Mus musculus 204-210 31665642-1 2019 The mechanistic target of rapamycin complex 2 (mTORC2) coordinates cell proliferation, survival, and metabolism with environmental inputs, yet how extracellular stimuli such as growth factors (GFs) activate mTORC2 remains enigmatic. Sirolimus 26-35 CREB regulated transcription coactivator 2 Mus musculus 47-53 31693882-2 2019 The kinase mechanistic target of rapamycin (mTOR) forms the enzymatic core of the highly conserved mTOR complexes mTORC1 and mTORC2. Sirolimus 33-42 CREB regulated transcription coactivator 2 Mus musculus 125-131 31062368-3 2019 Mammalian target of rapamycin complex 2 (mTORC2) has been implicated in cancer by regulating multiple AGC kinases, especially AKT proteins. Sirolimus 20-29 CREB regulated transcription coactivator 2 Mus musculus 41-47 31627299-3 2019 We previously established that irinotecan has antiangiogenic properties and it is known that new mammalian target of rapamycin (mTOR) catalytic AZD inhibitors, unlike rapamycin, target both mTORC1 and mTORC2. Sirolimus 117-126 CREB regulated transcription coactivator 2 Mus musculus 201-207 31619583-1 2019 The mechanistic target of rapamycin complex 2 (mTORC2) is a potentially novel and promising anticancer target due to its critical roles in proliferation, apoptosis, and metabolic reprogramming of cancer cells. Sirolimus 26-35 CREB regulated transcription coactivator 2 Mus musculus 47-53 31665642-1 2019 The mechanistic target of rapamycin complex 2 (mTORC2) coordinates cell proliferation, survival, and metabolism with environmental inputs, yet how extracellular stimuli such as growth factors (GFs) activate mTORC2 remains enigmatic. Sirolimus 26-35 CREB regulated transcription coactivator 2 Mus musculus 207-213 31577953-4 2019 These include rapamycin, which extends mouse lifespan yet induces insulin resistance by disrupting mTORC2 (mechanistic target of rapamycin complex 2). Sirolimus 14-23 CREB regulated transcription coactivator 2 Mus musculus 99-105 31373126-2 2019 mTOR is found in two protein complexes, mTORC1 and mTORC2, that have distinct components and substrates and are both inhibited by rapamycin, a macrolide drug that robustly extends lifespan in multiple species including worms and mice. Sirolimus 130-139 CREB regulated transcription coactivator 2 Mus musculus 51-57 31577953-4 2019 These include rapamycin, which extends mouse lifespan yet induces insulin resistance by disrupting mTORC2 (mechanistic target of rapamycin complex 2). Sirolimus 129-138 CREB regulated transcription coactivator 2 Mus musculus 99-105 31231029-3 2019 Rapamycin and its analogs target mTORC1 directly; however, chronic treatment in certain cell types and in vivo results in the inhibition of both mTORC1 and mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 156-162 31393061-2 2019 Phosphorylation of Akt Thr308 by PI3K-PDK1 and Akt Ser473 by mammalian target of rapamycin complex 2 (mTORC2) activates Akt. Sirolimus 81-90 CREB regulated transcription coactivator 2 Mus musculus 102-108 31475823-9 2019 mTOR inhibition by rapamycin totally blocked the stimulation of leucine and methionine on CRTC2 expression. Sirolimus 19-28 CREB regulated transcription coactivator 2 Mus musculus 90-95 31409770-8 2019 Rapamycin inhibited both mTORC1 and mTORC2 activation, whereas p62 siRNA inhibited only mTORC1 activation and maintained mTORC2 and Akt activation. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 36-42 31042058-10 2019 In conclusion, torin2 and sirolimus were equally effective in decreasing cyst burden and improving kidney function and mediated comparable effects on mTORC1 and mTORC2 signaling and proliferation in the Pkd1RC/RC kidney. Sirolimus 26-35 CREB regulated transcription coactivator 2 Mus musculus 161-167 31042058-2 2019 Proproliferative mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1 and mTORC2) are activated in the kidneys of mice with PKD. Sirolimus 39-48 CREB regulated transcription coactivator 2 Mus musculus 86-92 31092879-5 2019 Furthermore, simvastatin impaired the phosphorylation of Akt (Protein Kinase B) mainly at Ser473 and less at Thr308, indicating impaired activity of the mammalian Target of Rapamycin Complex 2 (mTORC2). Sirolimus 173-182 CREB regulated transcription coactivator 2 Mus musculus 194-200 30795552-4 2019 Mammalian (or mechanistic) target of rapamycin (mTOR) is a conserved serine/threonine kinase belonging to the phosphatidylinositol 3-kinase (PI3K)-related kinase family (PIKK) and resides in two distinct signalling complexes named mTORC1, involved in mRNA translation and protein synthesis and mTORC2 that controls cell survival and migration. Sirolimus 37-46 CREB regulated transcription coactivator 2 Mus musculus 294-300 31182914-8 2019 Mechanistically, the feedback activation of SGK3 by rapamycin was dependent on hVps34 and mTORC2, and reactivated mTORC1/4EBP1 axis by phosphorylating TSC2. Sirolimus 52-61 CREB regulated transcription coactivator 2 Mus musculus 90-96 30362509-3 2019 The expression of peroxisome proliferator-activated receptor gamma (PPARgamma), and mechanistic target of rapamycin complex 2 (mTORC2) were decreased in the livers of iAs-treated mice. Sirolimus 106-115 CREB regulated transcription coactivator 2 Mus musculus 127-133 30808817-5 2019 Glycolytic metabolism promoted the translocation of hexokinase-II to mitochondria and the activation of mammalian target of rapamycin complex 2 (mTORC2). Sirolimus 124-133 CREB regulated transcription coactivator 2 Mus musculus 145-151 29424687-4 2018 We report the architecture of human mTORC2 at intermediate resolution, revealing a conserved binding site for accessory proteins on mTOR and explaining the structural basis for the rapamycin insensitivity of the complex. Sirolimus 181-190 CREB regulated transcription coactivator 2 Mus musculus 36-42 31840789-5 2019 Many protein associations and regulatory pathways for mTORC1 and mTORC2 in Dictyostelium have context similarity to mammalian cells and specificity to inhibition by the immunosuppressive drug rapamycin. Sirolimus 192-201 CREB regulated transcription coactivator 2 Mus musculus 65-71 30285764-15 2018 CONCLUSIONS: Menin is involved in regulatory mechanism between the two mTOR complexes, and its reduced expression is accompanied with increased mTORC2-Akt signaling, which consequently impairs anti-migratory effect of rapamycin. Sirolimus 218-227 CREB regulated transcription coactivator 2 Mus musculus 144-150 30258985-2 2018 Although rapamycin inhibits the two canonical mTOR complexes, mTORC1 and mTORC2, it often shows minimal benefit as an anticancer drug. Sirolimus 9-18 CREB regulated transcription coactivator 2 Mus musculus 73-79 29475988-8 2018 Importantly, suppression of mTORC2 for 24 h with rapamycin or everolimus or treatment with mTOR active-site inhibitors enhanced HLA-II Ab-stimulated phosphorylation of ERK. Sirolimus 49-58 CREB regulated transcription coactivator 2 Mus musculus 28-34 29731844-4 2018 The results demonstrated that combined treatment with rapamycin and resveratrol effectively inhibited cell viability in the MM1.S cell line through inhibition of the mTORC1 and mTORC2 signaling pathways, compared with resveratrol or rapamycin monotherapy. Sirolimus 54-63 CREB regulated transcription coactivator 2 Mus musculus 177-183 29348496-9 2018 These effects were totally abrogated by inhibition of cGMP-dependent protein kinase and mTORC1/2 by rapamycin. Sirolimus 100-109 CREB regulated transcription coactivator 2 Mus musculus 88-96 28934384-9 2017 Further, mutant PKCepsilon caused impaired mTORC2-dependent pAKT-S473 following rapamycin treatment. Sirolimus 80-89 CREB regulated transcription coactivator 2 Mus musculus 43-49 25855786-3 2015 Although rapamycin analogues, allosteric inhibitors that target only the mTORC1 complex, have shown some clinical activity, it is hypothesized that mTOR kinase inhibitors, blocking both mTORC1 and mTORC2 signaling, will have expanded therapeutic potential. Sirolimus 9-18 CREB regulated transcription coactivator 2 Mus musculus 197-203 33834090-5 2017 Among these are mammalian target of rapamycin complexes 1 and 2 (mTORC1/2) and their associated pathways, which function in mitochondrial control and maintenance. Sirolimus 36-45 CREB regulated transcription coactivator 2 Mus musculus 65-73 28035937-2 2017 Even less studied or understood in AD is mammalian target of rapamycin complex 2 (mTORC2) that influences cellular metabolism, in part through the regulations of Akt/PKB and SGK. Sirolimus 61-70 CREB regulated transcription coactivator 2 Mus musculus 82-88 27173058-5 2016 Both increased mTORC1 and decreased mTORC2 activities were reversed by semi-chronic rapamycin treatment. Sirolimus 84-93 CREB regulated transcription coactivator 2 Mus musculus 36-42 27173058-6 2016 Acute treatment of hippocampal slices from AS mice with rapamycin or an S6K1 inhibitor, PF4708671, improved LTP, restored actin polymerization, and normalized mTORC1 and mTORC2 activity. Sirolimus 56-65 CREB regulated transcription coactivator 2 Mus musculus 170-176 26991739-6 2016 Treatment with 5 mg/kg rapamycin for 3 weeks to inhibit mTORC1 and mTORC2 fully reversed PH in SM22-TSC1(-/-) mice. Sirolimus 23-32 CREB regulated transcription coactivator 2 Mus musculus 67-73 26991739-7 2016 In chronically hypoxic mice and SM22-5HTT(+) mice exhibiting PH associated with mTORC1 and mTORC2 activation, PH was maximally attenuated by low-dose rapamycin associated with selective mTORC1 inhibition. Sirolimus 150-159 CREB regulated transcription coactivator 2 Mus musculus 91-97 27208895-3 2016 mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Sirolimus 98-107 CREB regulated transcription coactivator 2 Mus musculus 55-61 27208895-3 2016 mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Sirolimus 160-169 CREB regulated transcription coactivator 2 Mus musculus 55-61 27208895-4 2016 Over the past decade, it has become clear that although genetic and pharmacological inhibition of mTORC1 extends lifespan and delays aging, inhibition of mTORC2 has negative effects on mammalian health and longevity and is responsible for many of the negative side effects of rapamycin. Sirolimus 276-285 CREB regulated transcription coactivator 2 Mus musculus 154-160 26463117-3 2016 While the beneficial effects of rapamycin are largely mediated by the inhibition of mTOR complex 1 (mTORC1), which is acutely sensitive to rapamycin, many of the negative side effects are mediated by the inhibition of a second mTOR-containing complex, mTORC2, which is much less sensitive to rapamycin. Sirolimus 32-41 CREB regulated transcription coactivator 2 Mus musculus 252-258 25968579-8 2015 Incubation with rapamycin and AZD8055 indicated that mammalian target of rapamycin complex (mTORC)2, but not mTORC1, also is required for LIF-stimulated glucose uptake. Sirolimus 16-25 CREB regulated transcription coactivator 2 Mus musculus 92-99 28746918-12 2017 Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway. Sirolimus 71-74 CREB regulated transcription coactivator 2 Mus musculus 31-37 28746918-12 2017 Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway. Sirolimus 71-74 CREB regulated transcription coactivator 2 Mus musculus 219-225 27838442-10 2017 Furthermore, our discovery that administration of rapamycin increased the activation of mTORC2 in microglial cells supports a reappraisal of the beneficial/adverse effects of rapamycin administration. Sirolimus 50-59 CREB regulated transcription coactivator 2 Mus musculus 88-94 28373901-8 2017 Rapamycin induced phosphorylation of AKT S473 (target of mTORC2) but abolished ribosomal protein S6 phosphorylation (target of mTORC1) after I/R. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 57-63 27019134-1 2016 Everolimus (EVR) is an orally-administered rapamycin analog that selectively inhibits the mammalian target of rapamycin (mTOR) kinase (mainly mTORC1 and likely mTORC2) and the related signaling pathway. Sirolimus 43-52 CREB regulated transcription coactivator 2 Mus musculus 160-166 26002629-0 2015 Rapamycin prevents cadmium-induced neuronal cell death via targeting both mTORC1 and mTORC2 pathways. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 85-91 26002629-9 2015 The findings indicate that rapamycin prevents Cd-induced neuronal cell death via suppressing both mTORC1 and mTORC2 pathways. Sirolimus 27-36 CREB regulated transcription coactivator 2 Mus musculus 109-115 25836987-9 2015 Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). Sirolimus 39-48 CREB regulated transcription coactivator 2 Mus musculus 275-281 25880554-9 2015 Use of specific estrogen receptor (ER)alpha- and ERbeta-agonists indicated involvement of both estrogen receptors (ER) in rapamycin effects on mTORC1 and mTORC2. Sirolimus 122-131 CREB regulated transcription coactivator 2 Mus musculus 154-160 25911189-7 2015 Rapamycin treatment restored phosphorylation of STAT3 and enhanced AKT phosphorylation (target of mTORC2), but significantly reduced ribosomal protein S6 phosphorylation (target of mTORC1) in the diabetic heart. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 98-104 25880554-0 2015 17ss-Estradiol regulates mTORC2 sensitivity to rapamycin in adaptive cardiac remodeling. Sirolimus 47-56 CREB regulated transcription coactivator 2 Mus musculus 25-31 25880554-7 2015 Under physiological in vivo conditions, rapamycin compromised mTORC2 function only in female, but not in male murine hearts. Sirolimus 40-49 CREB regulated transcription coactivator 2 Mus musculus 62-68 25797247-9 2015 Thus, induction of GSK3-dependent degradation of these oncogenic proteins is likely secondary to mTORC2 inhibition; this effect should be critical for rapamycin to exert its anticancer activity. Sirolimus 151-160 CREB regulated transcription coactivator 2 Mus musculus 97-103 25652038-3 2015 The mechanism leading to cell specificity of mTORC2 inhibition by rapamycin is not understood and is especially important because many of the negative metabolic side effects of rapamycin, reported in mouse studies and human clinical trials, have been attributed recently to mTORC2 inhibition. Sirolimus 66-75 CREB regulated transcription coactivator 2 Mus musculus 45-51 25652038-3 2015 The mechanism leading to cell specificity of mTORC2 inhibition by rapamycin is not understood and is especially important because many of the negative metabolic side effects of rapamycin, reported in mouse studies and human clinical trials, have been attributed recently to mTORC2 inhibition. Sirolimus 66-75 CREB regulated transcription coactivator 2 Mus musculus 274-280 25652038-3 2015 The mechanism leading to cell specificity of mTORC2 inhibition by rapamycin is not understood and is especially important because many of the negative metabolic side effects of rapamycin, reported in mouse studies and human clinical trials, have been attributed recently to mTORC2 inhibition. Sirolimus 177-186 CREB regulated transcription coactivator 2 Mus musculus 45-51 25652038-3 2015 The mechanism leading to cell specificity of mTORC2 inhibition by rapamycin is not understood and is especially important because many of the negative metabolic side effects of rapamycin, reported in mouse studies and human clinical trials, have been attributed recently to mTORC2 inhibition. Sirolimus 177-186 CREB regulated transcription coactivator 2 Mus musculus 274-280 25738366-10 2015 Our findings suggest that rapamycin inhibits mSin1 phosphorylation, which is independent of mTORC1 and mTORC2, but is possibly dependent on a new mTOR complex, which at least contains mTOR and mLST8. Sirolimus 26-35 CREB regulated transcription coactivator 2 Mus musculus 103-109 25788687-8 2015 Furthermore, inhibitory phosphorylation of rictor, a key regulatory/structural subunit of the mTORC2 complex, was increased in AS mice and decreased after rapamycin treatment. Sirolimus 155-164 CREB regulated transcription coactivator 2 Mus musculus 94-100 25340604-6 2015 The treatment with RPM, but not Torin 1, resulted in the enhanced activation of the mTORC2-Akt signaling pathway activation in livers after reperfusion. Sirolimus 19-22 CREB regulated transcription coactivator 2 Mus musculus 84-90 26323019-7 2015 The reduced level of PA sensitizes mTORC2 to rapamycin at tolerable nano-molar doses leading reduced Akt phosphorylation and apoptosis. Sirolimus 45-54 CREB regulated transcription coactivator 2 Mus musculus 35-41 26323019-8 2015 This study reveals how the use of AICAR enhances the efficacy of rapamycin such that rapamycin at low nano-molar doses can suppress mTORC2 and induce apoptosis in human cancer cells at doses that are clinically tolerable. Sirolimus 65-74 CREB regulated transcription coactivator 2 Mus musculus 132-138 25340604-10 2015 CONCLUSION: Rapamycin protected livers from IRI by both autophagy and mTORC2-Akt activation mechanisms. Sirolimus 12-21 CREB regulated transcription coactivator 2 Mus musculus 70-76 24962700-3 2014 Although mTOR was originally discovered as a target protein of rapamycin, a natural macrolide immunosuppressant, rapamycin mainly inhibits the kinase activity of mTORC1, whereas mTORC2 is affected to a much lesser extent. Sirolimus 63-72 CREB regulated transcription coactivator 2 Mus musculus 178-184 25711103-4 2014 It exists in two mTOR protein complexes mTORC1 and mTORC2 with various sensitivity to the inhibitory effect of rapamycin. Sirolimus 111-120 CREB regulated transcription coactivator 2 Mus musculus 51-57 24557881-12 2014 Although rapamycin blocks Rps6-dependent mTORC2 activation, mTORC2 is still activated by an alternative signaling pathway, demonstrating the redundancy in cardioprotective signaling. Sirolimus 9-18 CREB regulated transcription coactivator 2 Mus musculus 41-47 24683191-5 2014 Rapamycin inhibited mTORC1 and enhanced mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 40-46 24516119-0 2014 Rapamycin antagonizes TNF induction of VCAM-1 on endothelial cells by inhibiting mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 81-87 24580843-6 2014 These results suggest that everolimus is more effective than sirolimus at antagonizing both mTORC1 and mTORC2, the latter of which is critical in endothelial cell functional changes leading to TV in solid organ transplantation after HLA I crosslinking. Sirolimus 61-70 CREB regulated transcription coactivator 2 Mus musculus 103-109 24504412-8 2014 Additionally, rapamycin prevented the denervation-induced upregulation of the mTORC2 substrates Akt and SGK. Sirolimus 14-23 CREB regulated transcription coactivator 2 Mus musculus 78-84 24516119-7 2014 In vivo, rapamycin inhibited mTORC2 activity and potentiated activation of ERK1/2. Sirolimus 9-18 CREB regulated transcription coactivator 2 Mus musculus 29-35 24462769-8 2014 In addition, chronic treatment with rapamycin, a condition known to interfere with assembly of mTORC2, reduces the interaction between Gbetagamma and mTOR and the phosphorylation of AKT; whereas overexpression of Galphai interfered with the effect of Gbetagamma as promoter of p70S6K and AKT phosphorylation. Sirolimus 36-45 CREB regulated transcription coactivator 2 Mus musculus 95-101 23339165-10 2013 In contrast to males, both mTORCs were decreased by rapamycin, in particular mTORC2 by 60%. Sirolimus 52-61 CREB regulated transcription coactivator 2 Mus musculus 77-83 24404143-11 2014 Those results suggested that mTOR Complex 1 (mTORC1) rather than mTORC2 was inhibited by rapamycin. Sirolimus 89-98 CREB regulated transcription coactivator 2 Mus musculus 65-71 24108520-6 2013 Rapamycin increased phosphorylation of raptor at Ser792 and decreased phosphorylation of rictor at Thr1135, suggesting that both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) are involved in GLT-1 expression. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 173-179 24078700-3 2013 In this study, we demonstrate that aging increases TORC2 signaling in murine CD4 T cells, a change blocked by long-term exposure to rapamycin, suggesting that functional defects may be the result of enhanced TORC2 function. Sirolimus 132-141 CREB regulated transcription coactivator 2 Mus musculus 51-56 24078700-3 2013 In this study, we demonstrate that aging increases TORC2 signaling in murine CD4 T cells, a change blocked by long-term exposure to rapamycin, suggesting that functional defects may be the result of enhanced TORC2 function. Sirolimus 132-141 CREB regulated transcription coactivator 2 Mus musculus 208-213 23792225-3 2013 The modest clinical anticancer activity of conventional mTOR allosteric inhibitors, rapamycin and its analogs (rapalogs), which preferentially inhibit mTORC1, in most types of cancer, has encouraged great efforts to develop mTOR kinase inhibitors (TORKinibs) that inhibit both mTORC1 and mTORC2, in the hope of developing a novel generation of mTOR inhibitors with better therapeutic efficacy than rapalogs. Sirolimus 84-93 CREB regulated transcription coactivator 2 Mus musculus 288-294 23991179-1 2013 Mammalian target of rapamycin complex 1 and 2 (mTORC1/2) are overactive in colorectal carcinomas; however, the first generation of mTOR inhibitors such as rapamycin have failed to show clinical benefits in treating colorectal carcinoma in part due to their effects only on mTORC1. Sirolimus 20-29 CREB regulated transcription coactivator 2 Mus musculus 47-55 23470622-2 2013 The mTOR pathway involves two independent complexes, mTORC1 and mTORC2, which phosphorylate S6 kinase (S6K) and serine/threonine kinase (Akt), respectively, and differ in their sensitivity to rapamycin. Sirolimus 192-201 CREB regulated transcription coactivator 2 Mus musculus 64-70 23297825-2 2013 The mammalian target of rapamycin complex 1 (mTORC1) is rapamycin-sensitive and mediates temporal control of cell growth by regulating several cellular processes, such as translation, transcription, and nutrient transport while the mammalian target of rapamycin complex 2 (mTORC2) is in sensitive to rapamycin and is involved in spatial control of cell growth via cytoskeleton regulation. Sirolimus 24-33 CREB regulated transcription coactivator 2 Mus musculus 273-279 25243120-4 2014 We show that chronic exposure of cells to rapamycin can inhibit mTORC2 pathway, and AKT will be destabilized by administration of the HSP90 inhibitor 17-allylamino-geldanamycin (17-AAG). Sirolimus 42-51 CREB regulated transcription coactivator 2 Mus musculus 64-70 23580240-0 2013 Concurrent inhibition of PI3K and mTORC1/mTORC2 overcomes resistance to rapamycin induced apoptosis by down-regulation of Mcl-1 in mantle cell lymphoma. Sirolimus 72-81 CREB regulated transcription coactivator 2 Mus musculus 41-47 23938603-8 2013 Rapamycin fully inhibited mTORC1 and partially inhibited mTORC2 activities, including the phosphorylation of Akt (serine 473) and PKCalpha, in vascular tumor cells. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 57-63 23863152-3 2013 On the other hand, the rapamycin-insensitive mTORC2 responds to the presence of growth factors such as insulin by phosphorylating Akt to promote its maturation and allosteric activation. Sirolimus 23-32 CREB regulated transcription coactivator 2 Mus musculus 45-51 22560223-5 2012 Rapamycin triggers a similar protective response in C. elegans and mice, but increases worm life span dependent upon SKN-1 and not DAF-16, apparently by interfering with TORC2 along with TORC1. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 170-175 22875246-0 2013 Rapamycin inhibits both motility through down-regulation of p-STAT3 (S727) by disrupting the mTORC2 assembly and peritoneal dissemination in sarcomatoid cholangiocarcinoma. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 93-99 24093774-3 2013 However, the dual nature of mTOR, existing in two multiprotein complexes mTORC1 and mTORC2 driven by different feedback loops, decreases the therapeutic effects of rapamycin, the specific mTOR inhibitor. Sirolimus 164-173 CREB regulated transcription coactivator 2 Mus musculus 84-90 22843885-6 2012 Phosphorylation of mTORC1 substrate, p70S6K at thr389 was reduced by rapamycin and pretreatment with rapamycin abrogated platelet-derived growth factor (PDGF)-induced activation of S6K, as well as that of mTORC2 substrate pAKT(Ser473). Sirolimus 69-78 CREB regulated transcription coactivator 2 Mus musculus 205-211 22843885-6 2012 Phosphorylation of mTORC1 substrate, p70S6K at thr389 was reduced by rapamycin and pretreatment with rapamycin abrogated platelet-derived growth factor (PDGF)-induced activation of S6K, as well as that of mTORC2 substrate pAKT(Ser473). Sirolimus 101-110 CREB regulated transcription coactivator 2 Mus musculus 205-211 22973301-0 2012 Rapamycin has a biphasic effect on insulin sensitivity in C2C12 myotubes due to sequential disruption of mTORC1 and mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 116-122 22973301-2 2012 We find that rapamycin has a clear biphasic effect on insulin sensitivity in C2C12 myotubes, with enhanced responsiveness during the first hour that declines to almost complete insulin resistance by 24-48 h. We and others have recently observed that chronic rapamycin treatment induces insulin resistance in rodents, at least in part due to disruption of mTORC2, an mTOR-containing complex that is not acutely sensitive to the drug. Sirolimus 13-22 CREB regulated transcription coactivator 2 Mus musculus 355-361 22973301-7 2012 Selective inhibition of mTORC1 or mTORC2 by shRNA-mediated knockdown of specific components (Raptor and Rictor, respectively) confirmed that mitochondrial effects of rapamycin are mTORC1-dependent, whereas insulin resistance was recapitulated only by knockdown of mTORC2. Sirolimus 166-175 CREB regulated transcription coactivator 2 Mus musculus 34-40 22973301-7 2012 Selective inhibition of mTORC1 or mTORC2 by shRNA-mediated knockdown of specific components (Raptor and Rictor, respectively) confirmed that mitochondrial effects of rapamycin are mTORC1-dependent, whereas insulin resistance was recapitulated only by knockdown of mTORC2. Sirolimus 166-175 CREB regulated transcription coactivator 2 Mus musculus 264-270 22973301-8 2012 Thus, mTORC2 disruption, rather than inhibition of mitochondria, causes insulin resistance in rapamycin-treated myotubes, and this system may serve as a useful model to understand the effects of rapamycin on mTOR signaling in vivo. Sirolimus 94-103 CREB regulated transcription coactivator 2 Mus musculus 6-12 22314813-0 2012 Rapamycin toxicity in MIN6 cells and rat and human islets is mediated by the inhibition of mTOR complex 2 (mTORC2). Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 107-113 22314813-7 2012 Although rapamycin acutely inhibited mTOR complex 1 (mTORC1), the toxic effects of rapamycin were more closely correlated to the dissociation and inactivation of mTORC2 and the inhibition of PKB. Sirolimus 83-92 CREB regulated transcription coactivator 2 Mus musculus 162-168 22314813-9 2012 Moreover, the selective inactivation of mTORC2 using siRNA directed towards rapamycin-insensitive companion of target of rapamycin (RICTOR), mimicked the toxic effects of chronic rapamycin treatment. Sirolimus 76-85 CREB regulated transcription coactivator 2 Mus musculus 40-46 22314813-10 2012 CONCLUSIONS/INTERPRETATION: This report provides evidence that rapamycin toxicity is mediated by the inactivation of mTORC2 and the inhibition of PKB and thus reveals the molecular basis of rapamycin toxicity and the essential role of mTORC2 in maintaining beta cell function and survival. Sirolimus 63-72 CREB regulated transcription coactivator 2 Mus musculus 117-123 22314813-10 2012 CONCLUSIONS/INTERPRETATION: This report provides evidence that rapamycin toxicity is mediated by the inactivation of mTORC2 and the inhibition of PKB and thus reveals the molecular basis of rapamycin toxicity and the essential role of mTORC2 in maintaining beta cell function and survival. Sirolimus 63-72 CREB regulated transcription coactivator 2 Mus musculus 235-241 22314813-10 2012 CONCLUSIONS/INTERPRETATION: This report provides evidence that rapamycin toxicity is mediated by the inactivation of mTORC2 and the inhibition of PKB and thus reveals the molecular basis of rapamycin toxicity and the essential role of mTORC2 in maintaining beta cell function and survival. Sirolimus 190-199 CREB regulated transcription coactivator 2 Mus musculus 117-123 22457328-2 2012 By assembling with unique and shared partner proteins, mTOR forms the catalytic core of at least two complexes, mTOR complex 1 (mTORC1) and mTORC2, that show differential sensitivity to the allosteric mTOR inhibitor rapamycin and that phosphorylate distinct substrates to modulate cell growth, proliferation, survival, and metabolism in response to diverse environmental cues. Sirolimus 216-225 CREB regulated transcription coactivator 2 Mus musculus 140-146 22407942-2 2012 Prolonged treatment with rapamycin inhibits mTOR complex 2 (mTORC2) activity, and both the mTORC1-mediated S6K1 and 4E-BP1/eIF4E pathways are essential for TORC2-mediated RhoA, Cdc42, and Rac1 expression during cell motility and F-actin reorganization. Sirolimus 25-34 CREB regulated transcription coactivator 2 Mus musculus 60-66 22407942-2 2012 Prolonged treatment with rapamycin inhibits mTOR complex 2 (mTORC2) activity, and both the mTORC1-mediated S6K1 and 4E-BP1/eIF4E pathways are essential for TORC2-mediated RhoA, Cdc42, and Rac1 expression during cell motility and F-actin reorganization. Sirolimus 25-34 CREB regulated transcription coactivator 2 Mus musculus 61-66 22461615-0 2012 Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 52-58 22461615-3 2012 We demonstrate that rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was required for the insulin-mediated suppression of hepatic gluconeogenesis. Sirolimus 20-29 CREB regulated transcription coactivator 2 Mus musculus 63-69 22461615-5 2012 Thus, mTORC2 disruption is an important mediator of the effects of rapamycin in vivo. Sirolimus 67-76 CREB regulated transcription coactivator 2 Mus musculus 6-12 22125063-6 2012 Moreover, the mTORC2 complex components rictor and sin1 are dephosphorylated and dynamically distributed between the cytoplasm and the nucleus upon long-term treatment with the mTOR-inhibitor rapamycin. Sirolimus 192-201 CREB regulated transcription coactivator 2 Mus musculus 14-20 21557327-4 2011 mTOR exists in two distinct complexes-mTORC1 and mTORC2 that differ in their components and sensitivity to rapamycin. Sirolimus 107-116 CREB regulated transcription coactivator 2 Mus musculus 49-55 23185517-2 2012 mTORC1 inhibitors have shown limited efficacy in the clinic, largely attributed to the reactivation of Akt due to rapamycin induced mTORC2 activity. Sirolimus 114-123 CREB regulated transcription coactivator 2 Mus musculus 132-138 21672148-0 2011 Rapamycin-induced hypophosphatemia and insulin resistance are associated with mTORC2 activation and Klotho expression. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 78-84 21672148-6 2011 Rapamycin treatment of an immortalized proximal tubular cell line induced the expression of Klotho, the phosphorylation of AKT in Ser473, downstream target of mTORC2 and the expression of RICTOR, mTORC2 main component. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 159-165 21672148-6 2011 Rapamycin treatment of an immortalized proximal tubular cell line induced the expression of Klotho, the phosphorylation of AKT in Ser473, downstream target of mTORC2 and the expression of RICTOR, mTORC2 main component. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 196-202 21576371-7 2011 Importantly, nonefficacious concentrations of an ATP-competitive mTOR inhibitor can be combined with rapamycin to synergistically inhibit mTORC1 and activate autophagy but leave mTORC2 signaling intact. Sirolimus 101-110 CREB regulated transcription coactivator 2 Mus musculus 178-184 21357504-8 2011 Rapamycin pretreatment also significantly increased PO-induced Akt phosphorylation at S473, a finding confirmed in cardiomyocytes in vitro to be downstream of mTORC2. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 159-165 21357511-8 2011 We conclude that rapamycin inhibits H2O2-induced loss of vascular contractility, likely through an mTORC2-calcineurin pathway. Sirolimus 17-26 CREB regulated transcription coactivator 2 Mus musculus 99-105 20943770-8 2011 On immunoblot of kidney, phosphorylated (Ser473) Akt (p-Akt), a marker of mTORC2 activity, was increased in female Cy/+ rats treated with rapamycin. Sirolimus 138-147 CREB regulated transcription coactivator 2 Mus musculus 74-80 21177249-6 2011 Enhanced Akt phosphorylation was not due to activation of phosphatidylinositol 3-kinase but due to activation of mammalian target of rapamycin complex 2 (mTORC2) by PINK1. Sirolimus 133-142 CREB regulated transcription coactivator 2 Mus musculus 154-160 21048785-3 2011 Here, we studied the effect of targeting the PI3K/mTORC1/mTORC2 pathway by PI-103 and rapamycin in melanoma cells and in a melanoma mouse model. Sirolimus 86-95 CREB regulated transcription coactivator 2 Mus musculus 57-63 19270529-9 2009 Since mTORC2 is likely more critical for survival signals in cancer cells, the recent findings suggest new strategies for enhancing the efficacy of rapamycin-based therapeutic approaches in cancer cells. Sirolimus 148-157 CREB regulated transcription coactivator 2 Mus musculus 6-12 20884880-7 2010 SGK-1 activation in response to stretch is blocked by insulin-like growth factor (IGF)-1 receptor inhibitor and mammalian target of rapamycin complex (mTORC)2 inhibitor (Ku-0063794) but not mTORC1 inhibitor (rapamycin). Sirolimus 132-141 CREB regulated transcription coactivator 2 Mus musculus 151-158 20496258-2 2010 The discovery of the involvement of rapamycin-insensitive mTOR complex 2 (mTORC2) in the activation of Akt, combined with the limited clinical antitumor activity of mTOR complex 1 (mTORC1)-directed rapamycin analogs, have led to the discovery of ATP-competitive selective inhibitors of the mTOR kinase that inhibit the function of both mTORC1 and mTORC2. Sirolimus 36-45 CREB regulated transcription coactivator 2 Mus musculus 74-80 20116405-1 2010 Inhibition of mTORC1 with the mTOR inhibitor rapamycin may lead to an induction of Akt phosphorylation in cancer cells via mTORC2 activation. Sirolimus 45-54 CREB regulated transcription coactivator 2 Mus musculus 123-129 20022946-8 2010 Although insulin stimulates both mTORC1- and mTORC2-associated mTOR Ser(P)-2481 in a phosphatidylinositol 3-kinase-dependent manner, rapamycin acutely inhibits insulin-stimulated mTOR Ser(P)-2481 in mTORC1 but not mTORC2. Sirolimus 133-142 CREB regulated transcription coactivator 2 Mus musculus 45-51 20022946-8 2010 Although insulin stimulates both mTORC1- and mTORC2-associated mTOR Ser(P)-2481 in a phosphatidylinositol 3-kinase-dependent manner, rapamycin acutely inhibits insulin-stimulated mTOR Ser(P)-2481 in mTORC1 but not mTORC2. Sirolimus 133-142 CREB regulated transcription coactivator 2 Mus musculus 214-220 20022946-10 2010 These data suggest that mTORC1- and likely mTORC2-associated mTOR Ser-2481 autophosphorylation directly monitors intrinsic mTORC-specific catalytic activity and reveal that rapamycin inhibits mTORC1 signaling in vivo by reducing mTORC1 catalytic activity. Sirolimus 173-182 CREB regulated transcription coactivator 2 Mus musculus 43-49 19641186-0 2009 Inhibition of histone deacetylase overcomes rapamycin-mediated resistance in diffuse large B-cell lymphoma by inhibiting Akt signaling through mTORC2. Sirolimus 44-53 CREB regulated transcription coactivator 2 Mus musculus 143-149 19641186-4 2009 Subsequent investigations revealed that rapamycin also activated eIF4E and the mTORC2 target Akt, suggesting a potential mechanism of rapamycin resistance. Sirolimus 40-49 CREB regulated transcription coactivator 2 Mus musculus 79-85 19641186-5 2009 Furthermore, knockdown of the mTORC2 component rictor, but not the mTORC1 component raptor, inhibited rapamycin-induced Akt phosphorylation in lymphoma cells. Sirolimus 102-111 CREB regulated transcription coactivator 2 Mus musculus 30-36 19641186-8 2009 This is the first demonstration that a HDI such as LBH can overcome rapamycin resistance through a phosphatase that antagonizes mTORC2 activation. Sirolimus 68-77 CREB regulated transcription coactivator 2 Mus musculus 128-134 19443844-8 2009 Rapamycin decreased phosphorylation of both Akt and S6, suggesting that both the TORC1 and TORC2 pathways are impacted. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 91-96 19379082-4 2009 However, in recent preclinical studies a sustained exposure of cancer cells to rapamycin has been shown to inhibit the function of both mTORC1 and mTORC2 complexes. Sirolimus 79-88 CREB regulated transcription coactivator 2 Mus musculus 147-153 21228924-1 2010 The mammalian target of rapamycin (MTOR) assembles into two distinct complexes: mTOR complex 1 (mTORC1) is predominantly cytoplasmic and highly responsive to rapamycin, whereas mTOR complex 2 (mTORC2) is both cytoplasmic and nuclear, and relatively resistant to rapamycin. Sirolimus 24-33 CREB regulated transcription coactivator 2 Mus musculus 193-199 20512842-0 2010 Rapamycin regulates Akt and ERK phosphorylation through mTORC1 and mTORC2 signaling pathways. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 67-73 20512842-2 2010 In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin-mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors. Sirolimus 72-81 CREB regulated transcription coactivator 2 Mus musculus 62-68 20512842-4 2010 We found that low concentrations rapamycin increased Akt and ERK phosphorylation through a mTORC1-dependent mechanism because knockdowned raptor induced the activation of Akt and ERK, but higher doses of rapamycin inhibited Akt and ERK phosphorylation mainly via the mTORC2 signaling pathway because that the silencing of rictor led to the inhibition of Akt and ERK phosphorylation. Sirolimus 33-42 CREB regulated transcription coactivator 2 Mus musculus 267-273 20512842-7 2010 Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin-mediated phosphorylation of Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin-based therapeutic approaches in cancer cells. Sirolimus 86-95 CREB regulated transcription coactivator 2 Mus musculus 31-37 19443844-3 2009 Rapamycin (0.5 mg/kg/d) effectively inhibited mTOR and downstream S6K1 signaling and partially inhibited Akt signaling, likely through effects on TORC2. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 146-151 19270529-5 2009 Second, the efficacy of rapamycin is dependent on the level of phosphatidic acid (PA), which is required for the assembly of both mTORC1 and mTORC2 complexes. Sirolimus 24-33 CREB regulated transcription coactivator 2 Mus musculus 141-147 19270529-8 2009 A practical outcome of the recent study is that if PA levels are suppressed, mTORC2 becomes sensitive to concentrations of rapamycin that can be achieved clinically. Sirolimus 123-132 CREB regulated transcription coactivator 2 Mus musculus 77-83 19244117-7 2009 Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Sirolimus 66-75 CREB regulated transcription coactivator 2 Mus musculus 44-50 19244117-7 2009 Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Sirolimus 66-75 CREB regulated transcription coactivator 2 Mus musculus 90-96 19244117-7 2009 Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Sirolimus 118-127 CREB regulated transcription coactivator 2 Mus musculus 44-50 19244117-7 2009 Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Sirolimus 118-127 CREB regulated transcription coactivator 2 Mus musculus 90-96 19244117-7 2009 Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Sirolimus 118-127 CREB regulated transcription coactivator 2 Mus musculus 90-96 19244117-7 2009 Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Sirolimus 118-127 CREB regulated transcription coactivator 2 Mus musculus 44-50 19244117-7 2009 Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Sirolimus 118-127 CREB regulated transcription coactivator 2 Mus musculus 90-96 19244117-7 2009 Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Sirolimus 118-127 CREB regulated transcription coactivator 2 Mus musculus 90-96 19244117-8 2009 Thus, phospho-S2481 on mTOR serves as a biomarker for intact mTORC2 and its sensitivity to rapamycin. Sirolimus 91-100 CREB regulated transcription coactivator 2 Mus musculus 61-67 19244117-7 2009 Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Sirolimus 66-75 CREB regulated transcription coactivator 2 Mus musculus 90-96 19114562-0 2009 Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid: competition with rapamycin. Sirolimus 88-97 CREB regulated transcription coactivator 2 Mus musculus 25-31 19114562-8 2009 Suppressing PA production substantially increased the sensitivity of mTORC2 to rapamycin. Sirolimus 79-88 CREB regulated transcription coactivator 2 Mus musculus 69-75 19114562-9 2009 Data provided here demonstrate a PA requirement for the stabilization of both mTORC1 and mTORC2 complexes and reveal a mechanism for the inhibitory effect of rapamycin on mTOR. Sirolimus 158-167 CREB regulated transcription coactivator 2 Mus musculus 89-95 19114562-10 2009 This study also suggests that by suppressing PLD activity, mTORC2 could be targeted therapeutically with rapamycin. Sirolimus 105-114 CREB regulated transcription coactivator 2 Mus musculus 59-65 18812319-2 2008 mTOR forms two functionally distinct complexes, termed the mTOR complex 1 (mTORC1) and 2 (mTORC2); only the former of which is inhibited by rapamycin. Sirolimus 140-149 CREB regulated transcription coactivator 2 Mus musculus 90-96 18945681-5 2008 mTOR exists in two complexes, mTORC1 and mTORC2, which are differentially sensitive to rapamycin. Sirolimus 87-96 CREB regulated transcription coactivator 2 Mus musculus 41-47 18776922-6 2008 Inhibition of both mTORC1 and mTORC2 by rapamycin-induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1, but not mTORC2. Sirolimus 40-49 CREB regulated transcription coactivator 2 Mus musculus 30-36 19018001-4 2008 We found that rapamycin, which blocks mTORC1 and mTORC2 signaling, inhibited sCD40L-mediated transactivation of VEGF. Sirolimus 14-23 CREB regulated transcription coactivator 2 Mus musculus 49-55 18250144-7 2008 Under the conditions adopted, rapamycin inhibited both mammalian target-of-rapamycin complexes (mTORC1 and mTORC2), as indicated by the reduced amount of raptor and rictor bound to mTOR in immunoprecipitates and by the marked hypophosphorylation of protein S6 kinase I (p70S6K) and Akt, determined by western blotting. Sirolimus 30-39 CREB regulated transcription coactivator 2 Mus musculus 107-113 18614546-0 2008 Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: rapamycin triggers dephosphorylation and delocalization of the mTORC2 components rictor and sin1. Sirolimus 81-90 CREB regulated transcription coactivator 2 Mus musculus 73-79 18614546-0 2008 Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: rapamycin triggers dephosphorylation and delocalization of the mTORC2 components rictor and sin1. Sirolimus 81-90 CREB regulated transcription coactivator 2 Mus musculus 144-150 17179228-0 2007 Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 29-35 16870609-4 2006 mTORC2 is rapamycin-insensitive and likely regulates actin organization and activates Akt/protein kinase B. Sirolimus 10-19 CREB regulated transcription coactivator 2 Mus musculus 0-6 16603397-0 2006 Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Sirolimus 10-19 CREB regulated transcription coactivator 2 Mus musculus 39-45 16603397-5 2006 Here we show that rapamycin inhibits the assembly of mTORC2 and that, in many cell types, prolonged rapamycin treatment reduces the levels of mTORC2 below those needed to maintain Akt/PKB signaling. Sirolimus 18-27 CREB regulated transcription coactivator 2 Mus musculus 53-59 16603397-5 2006 Here we show that rapamycin inhibits the assembly of mTORC2 and that, in many cell types, prolonged rapamycin treatment reduces the levels of mTORC2 below those needed to maintain Akt/PKB signaling. Sirolimus 18-27 CREB regulated transcription coactivator 2 Mus musculus 142-148 16603397-5 2006 Here we show that rapamycin inhibits the assembly of mTORC2 and that, in many cell types, prolonged rapamycin treatment reduces the levels of mTORC2 below those needed to maintain Akt/PKB signaling. Sirolimus 100-109 CREB regulated transcription coactivator 2 Mus musculus 53-59 16603397-5 2006 Here we show that rapamycin inhibits the assembly of mTORC2 and that, in many cell types, prolonged rapamycin treatment reduces the levels of mTORC2 below those needed to maintain Akt/PKB signaling. Sirolimus 100-109 CREB regulated transcription coactivator 2 Mus musculus 142-148 34699314-6 2021 LINC00998 was mainly located in the cytoplasm, in which interacted with ZFP36 ring finger protein (ZFP36), a mRNA destabilizing factor, resulting in increased decay of mammalian target of rapamycin complex 2 (mTORC2), a well-known proto-oncogene in AML. Sirolimus 188-197 CREB regulated transcription coactivator 2 Mus musculus 209-215 15467718-6 2004 Like yeast TORC2, mTORC2 is rapamycin insensitive and seems to function upstream of Rho GTPases to regulate the actin cytoskeleton. Sirolimus 28-37 CREB regulated transcription coactivator 2 Mus musculus 18-24 33033115-3 2020 Recently, the mechanistic target of rapamycin complex 2 (mTORC2) was identified as an evolutionarily conserved Ras effector. Sirolimus 36-45 CREB regulated transcription coactivator 2 Mus musculus 57-63 34866401-1 2022 In mice, exercise is suggested to activate the mechanistic target of rapamycin complex 2 (mTORC2) in skeletal muscle, and mTORC2 is required for normal muscle glucose uptake during exercise. Sirolimus 69-78 CREB regulated transcription coactivator 2 Mus musculus 90-96 34866401-1 2022 In mice, exercise is suggested to activate the mechanistic target of rapamycin complex 2 (mTORC2) in skeletal muscle, and mTORC2 is required for normal muscle glucose uptake during exercise. Sirolimus 69-78 CREB regulated transcription coactivator 2 Mus musculus 122-128 34949833-3 2022 Here, using a mouse model of acute infection with lymphocytic choriomeningitis virus (LCMV), we found that the serine/threonine kinase complex mammalian target of rapamycin complex 2 (mTORC2) is critical for the long-term persistence of virus-specific memory CD4+ T cells. Sirolimus 163-172 CREB regulated transcription coactivator 2 Mus musculus 184-190 34626605-9 2021 Further, these acetate molecules regulate genes involved in mammalian target of rapamycin complex 2 (mTORC2) such as mammalian stress-activated protein kinase-interacting protein (mSIN1), protein observed with Rictor 2 (Protor 2), and protein kinase C alpha (PKCalpha). Sirolimus 80-89 CREB regulated transcription coactivator 2 Mus musculus 101-107 34805133-1 2021 Mechanistic Target of Rapamycin Complex 2 (mTORC2) regulates placental amino acid and folate transport. Sirolimus 22-31 CREB regulated transcription coactivator 2 Mus musculus 43-49 34858182-6 2021 Phosphorylation of both PDGFRalpha and PDGFRbeta was increased in hPASMCs after treatment with rapamycin for 48 and 72 h. Based on co-immunoprecipitation studies, longer exposure to rapamycin (24-72 h) significantly inhibited the binding of mTOR to Rictor, mechanistically suggesting mTORC2 inhibition by rapamycin. Sirolimus 95-104 CREB regulated transcription coactivator 2 Mus musculus 284-290 34858182-6 2021 Phosphorylation of both PDGFRalpha and PDGFRbeta was increased in hPASMCs after treatment with rapamycin for 48 and 72 h. Based on co-immunoprecipitation studies, longer exposure to rapamycin (24-72 h) significantly inhibited the binding of mTOR to Rictor, mechanistically suggesting mTORC2 inhibition by rapamycin. Sirolimus 182-191 CREB regulated transcription coactivator 2 Mus musculus 284-290 34858182-6 2021 Phosphorylation of both PDGFRalpha and PDGFRbeta was increased in hPASMCs after treatment with rapamycin for 48 and 72 h. Based on co-immunoprecipitation studies, longer exposure to rapamycin (24-72 h) significantly inhibited the binding of mTOR to Rictor, mechanistically suggesting mTORC2 inhibition by rapamycin. Sirolimus 305-314 CREB regulated transcription coactivator 2 Mus musculus 284-290 34858182-10 2021 Conclusion: Prolonged rapamycin treatment activates PDGFR signaling, in part, via mTORC2 inhibition. Sirolimus 22-31 CREB regulated transcription coactivator 2 Mus musculus 82-88 34551966-8 2021 Our results show that TLR-4-induced IFN-gamma production is regulated by the ribosomal protein S6 kinase (p70S6K) through the activation of PI3K, the mammalian target of rapamycin complex 1/2 (mTORC1/2), and the JNK MAPK pathways. Sirolimus 170-179 CREB regulated transcription coactivator 2 Mus musculus 193-201 34757123-6 2022 The mTOR inhibitor, rapamycin, completely abolished activation of mTORC1 and mTORC2 after long term treatment with receptor antibodies. Sirolimus 20-29 CREB regulated transcription coactivator 2 Mus musculus 77-83 34769253-3 2021 AZD8055, an ATP-competitive mechanistic target of rapamycin complex 1/2 (mTORC1/2) inhibitor, was selected as a translational suppressor. Sirolimus 50-59 CREB regulated transcription coactivator 2 Mus musculus 73-81 34986526-7 2021 Compared with the model group, the differentiation level of Treg cells in the rapamycin group was significantly increased, the proliferation level of CD4CD25 T cells was decreased, and the phosphorylations of the mTORC1/2 substrates, S6 protein and Akt were decreased (all <0.05). Sirolimus 78-87 CREB regulated transcription coactivator 2 Mus musculus 213-221 34986526-8 2021 Rapamycin can promote the differentiation and function of Treg cells via inhibition of the mTORC1/2 signaling pathway. Sirolimus 0-9 CREB regulated transcription coactivator 2 Mus musculus 91-99 34650053-5 2021 Here we show that mammalian target of rapamycin complex 2 (mTORC2) is essential for the survival of experimental animals after ocular HSV-1 infection in vivo. Sirolimus 38-47 CREB regulated transcription coactivator 2 Mus musculus 59-65 34610303-2 2021 The serum- and glucocorticoid-regulated family of protein kinases (SGK) is activated downstream of mechanistic target of rapamycin complex 2 (mTORC2) in response to insulin in parallel to AKT. Sirolimus 121-130 CREB regulated transcription coactivator 2 Mus musculus 142-148 34155681-3 2021 Here, we demonstrated that Rictor, a key component of mechanistic target of rapamycin complex 2 (mTORC2), was crucial for TRAF6/TRAF3 expression in osteoclasts. Sirolimus 76-85 CREB regulated transcription coactivator 2 Mus musculus 97-103 34209274-4 2021 The mammalian target of the Rapamycin (mTOR) signaling pathway that acts via two distinct multiprotein complexes, mTORC1 and mTORC2, can affect oxidative stress. Sirolimus 28-37 CREB regulated transcription coactivator 2 Mus musculus 125-131 34585416-2 2022 Here, we show that mechanistic target of rapamycin complex 2 (mTORC2)-dependent Akt activation is instrumental for metabolic reprogramming at the early stages of macrophage-mediated immunity. Sirolimus 41-50 CREB regulated transcription coactivator 2 Mus musculus 62-68 34354602-11 2021 Rapalink-1 significantly decreased phosphorylated S6 and Akt to half the level of the control rats in the IR-C, which suggests that both of the mechanistic target of rapamycin complex 1 and 2 (mTORC1 and mTORC2) were inhibited. Sirolimus 166-175 CREB regulated transcription coactivator 2 Mus musculus 204-210 35219732-4 2022 A detailed description of signaling pathways of mTORC1 and mTORC2 that are inhibited by rapamycin and other mTOR inhibitor analogues is accentuated. Sirolimus 88-97 CREB regulated transcription coactivator 2 Mus musculus 59-65 35361526-3 2022 Recent findings snapped the pieces of the phosphorylation puzzle into place to unveil a process that involves a newly described motif (TOR interaction motif, TIM), a well-described kinase (mechanistic target of rapamycin complex 2 (mTORC2)), and an often-used mechanism (autophosphorylation) to prime PKC to signal. Sirolimus 211-220 CREB regulated transcription coactivator 2 Mus musculus 232-238 35579957-3 2022 Here, we showed that tissue inflammation-induced activation of the mammalian target of rapamycin complex 2 (mTORC2) triggers changes in the architecture of nociceptive terminals and leads to inflammatory pain. Sirolimus 87-96 CREB regulated transcription coactivator 2 Mus musculus 108-114 34130715-6 2021 The majority of the affected pathways are downstream targets of the mammalian target of rapamycin complex 2 (mTORC2), indicating that this stress-responsive complex plays a role in propagating the epigenetic memory of alcohol exposure through gestation. Sirolimus 88-97 CREB regulated transcription coactivator 2 Mus musculus 109-115 34103528-6 2021 Mechanistically, AKT1-R391 methylation cooperates with phosphatidylinositol 3,4,5 trisphosphate (PIP3) to relieve the pleckstrin homology (PH)-in conformation, leading to AKT1 membrane translocation and subsequent activation by phosphoinositide-dependent kinase-1 (PDK1) and the mechanistic target of rapamycin complex 2 (mTORC2). Sirolimus 301-310 CREB regulated transcription coactivator 2 Mus musculus 322-328 35488725-5 2022 However, sirolimus has not shown uniform effect, potentially due to its limited mTORC2 inhibition. Sirolimus 9-18 CREB regulated transcription coactivator 2 Mus musculus 80-86 35174167-4 2021 ARHGEF3 also binds the mammalian target of rapamycin complex 2 (mTORC2) and subsequently inhibits mTORC2 and Akt. Sirolimus 43-52 CREB regulated transcription coactivator 2 Mus musculus 64-70 35238644-5 2022 Herein, based on pharmacological and genetic interventions, we found that a high dose of sirolimus resulted in severe hearing loss by reducing the mTORC2/AKT signaling pathway in the cochlea. Sirolimus 89-98 CREB regulated transcription coactivator 2 Mus musculus 147-153 35174167-4 2021 ARHGEF3 also binds the mammalian target of rapamycin complex 2 (mTORC2) and subsequently inhibits mTORC2 and Akt. Sirolimus 43-52 CREB regulated transcription coactivator 2 Mus musculus 98-104 33444645-1 2021 Endocytosis plays an important role in the immune defence systems of invertebrates through the interaction between the mechanical target of rapamycin complex 2 (mTORC2) and the AGC kinase family. Sirolimus 140-149 CREB regulated transcription coactivator 2 Mus musculus 161-167 33976205-4 2021 While Tanc2-null mice show embryonic lethality, Tanc2-haploinsufficient mice survive but display mTORC1/2 hyperactivity accompanying synaptic and behavioral deficits reversed by mTOR-inhibiting rapamycin. Sirolimus 194-203 CREB regulated transcription coactivator 2 Mus musculus 97-105 33872697-1 2021 Activation of the protein kinase mechanistic target of rapamycin (mTOR) in both complexes 1 and 2 (mTORC1/2) in the liver is repressed during fasting and rapidly stimulated in response to a meal. Sirolimus 55-64 CREB regulated transcription coactivator 2 Mus musculus 99-107 33547375-1 2021 Rictor is a key component of the mammalian target of rapamycin complex 2 (mTORC2) and is required for Akt phosphorylation (Ser473). Sirolimus 53-62 CREB regulated transcription coactivator 2 Mus musculus 74-80 33674554-2 2021 In the present study, we found that both sham surgery and unilateral nephrectomy (UNX), which is used as a model of renal compensatory hypertrophy, in mice resulted in increased mammalian target of rapamycin complex 1/2 (mTORC1/2) in the remaining kidney. Sirolimus 198-207 CREB regulated transcription coactivator 2 Mus musculus 221-229 33452321-7 2021 Morphological and biochemical validation of autophagy markers in the cell model of 3-NPA revealed incomplete autophagy mediated by mechanistic Target of Rapamycin Complex 2 (mTORC2) pathway. Sirolimus 153-162 CREB regulated transcription coactivator 2 Mus musculus 174-180 32394479-3 2021 The mTOR protein is incorporated into two distinct complexes: mammalian target of Rapamycin complex 1 (mTORC1) and mammalian target of Rapamycin complex 2 (mTORC2). Sirolimus 135-144 CREB regulated transcription coactivator 2 Mus musculus 156-162 33378666-1 2020 The mechanistic target of rapamycin complex 2 (mTORC2) controls cell metabolism and survival in response to environmental inputs. Sirolimus 26-35 CREB regulated transcription coactivator 2 Mus musculus 47-53 33125102-3 2020 The present study thus aimed to investigate the effects of PTH(1-34) on the migration and adhesion of, and rictor/mammalian target of rapamycin complex 2 (mTORC2) signaling in BMSCs. Sirolimus 134-143 CREB regulated transcription coactivator 2 Mus musculus 155-161