ライフサイエンスコーパス: mTORC2

1 , AKT and the two mTOR complexes (mTORC1 and mTORC2).

2 g inhibition of the mTOR complex (mTORC1 and mTORC2).

3 mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).

4 e mechanistic target of rapamycin complex 2 (mTORC2).

5 , it has a minimal effect on mTOR complex 2 (mTORC2).

6 of mammalian target of rapamycin complex 2 (mTORC2).

7 hrough two multiprotein complexes, mTORC1 or mTORC2.

8 ls, with subsequent activation of mTORC1 and mTORC2.

9 hosphorylation at T308 via PI3K and S473 via mTORC2.

10 mTOR), existing in two complexes, mTORC1 and mTORC2.

11 gulated by distinct functions for mTORC1 and mTORC2.

12 thways through feedback mechanisms involving mTORC2.

13 c target of rapamycin complex 1 (mTORC1) and mTORC2.

14 and selective dual inhibitors of mTORC1 and mTORC2.

15 kinase that forms two complexes, mTORC1 and mTORC2.

16 inase complexes, mTOR complex 1 (mTORC1) and mTORC2.

17 naling complexes mTOR complex 1 (mTORC1) and mTORC2.

18 (DC), little is known about the function of mTORC2.

19 endent complexes, mTOR complex (mTORC) 1 and mTORC2.

20 h feedback inhibition of Akt, a substrate of mTORC2.

21 ation of AMOTL2 as a candidate substrate for mTORC2.

22 and forms two distinct complexes: mTORC1 and mTORC2.

23 these lesions, consistent with activation of mTORC2.

24 inhibitors (TOR-KIs) inhibit both mTORC1 and mTORC2.

25 ment and function of iNKT cells regulated by mTORC2.

26 AMOTL2 is phosphorylated at serine 760 by mTORC2.

27 h stabilizes both mTOR complexes: mTORC1 and mTORC2.

28 ase forms two distinct complexes: mTORC1 and mTORC2.

29 eatment with a small molecule that activates mTORC2 (A-443654) reverses long-term memory (LTM) defici

30 reast cancer models, but the significance of mTORC2-activated Akt signaling in this setting remains u

31 o be of high physiological relevance because mTORC2 activation was observed at the cellular, tissue,

32 hatase and tensin homolog (Pten) upregulated mTORC2 activity and enhanced NKT17 generation, but conco

33 creased lipogenesis correlated with elevated mTORC2 activity and HCC in human patients.

34 nd functionally important for suppression of mTORC2 activity and invasion.

35 nslation, and consequently failed to repress mTORC2 activity and invasion.

36 of Akt enhanced rictor levels and increased mTORC2 activity as evidenced by increased formation of m

37 /HuR signaling cascade resulting in enhanced mTORC2 activity in these tumors.

38 in a feed-forward cascade in which continued mTORC2 activity is able to drive Rictor expression.

39 pproaches, we demonstrate that inside cells, mTORC2 activity localizes to the plasma membrane, mitoch

40 dicate that the imbalance between mTORC1 and mTORC2 activity may contribute to synaptic pathology and

41 1 influenced CD8+ T cell effector responses, mTORC2 activity regulated CD8+ T cell memory.

42 These data establish that mTORC2 activity restrains conventional DC proinflammator

43 e for a feed-forward loop mechanism by which mTORC2 activity stimulates Rictor translational efficien

44 calization could contribute to regulation of mTORC2 activity toward Akt.

45 ation of DEPTOR, an endogenous antagonist of mTORC2 activity.

46 ion and signaling, consistent with decreased mTORC2 activity.

47 gulation by growth factors of the endogenous mTORC2 activity.

48 the mammalian target of rapamycin complex 2 (mTORC2)/Akt signaling pathway is highly elevated in MFN2

49 mal cancer cells deploy the PI3K-independent mTORC2-AKT axis in response to strong death stimuli.

50 Our results showed that RICTOR/MTORC2-AKT can integrate convergent hormonal and metabol

51 MTORC2-AKT is a key regulator of carbohydrate metabolism

52 tly, little is known about the regulation of MTORC2-AKT or FOXO1 by TH.

53 ccurs via nutritional activation of the PI3K-mTORC2-Akt pathway.

54 ke growth factor 2 (Igf2) that activates the mTORC2-Akt signaling cascade during osteoblast different

55 s LPS/TLR4 signals in leukocytes through the mTORC2-Akt-FoxO signaling axis.

56 of persistent activation of the class I PI3K/mTORC2/AKT pathway and an increase of the antiproliferat

57 Moreover, we demonstrate that mTORC2/AKT signaling activates HSF1 resulting in a feed-

58 Pten(ptKO) mice also attenuated class I PI3K/mTORC2/AKT signaling and reduced the size of enlarged ki

59 endent roles for EGFR-modulated class I PI3K/mTORC2/AKT signaling in the normal adaptation of kidney

60 synthesis and proliferation of ASMCs via the mTORC2/Akt signalling pathway, thereby regulating airway

61 pivotal role for OTUD7B in the activation of mTORC2/AKT signalling, genetic deletion of Otud7b in mic

62 tes results in activation of both mTORC1 and mTORC2/Akt, inducing rapid melanoma formation in mice.

63 gaged by the type II IFN receptor, involving mTORC2/AKT-mediated downstream regulation of mTORC1 and

64 mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosur

65 Finally, an analysis of mTORC2/AMOTL2/YAP activities in primary GBM samples supp

66 Cdkn2a loss is associated with mTORC2 and Akt activation in human and murine melanocyti

67 regulate Akt by downregulating complexes of mTORC2 and CDK2/cyclin A2 and upregulating PSMB6, which

68 th factor receptors and upstream of PDK1 and mTORC2 and copurifies with PI3K in immunoprecipitation a

69 ivity as evidenced by increased formation of mTORC2 and elevated phosphorylation of Akt, SGK1, and PK

70 ntestinal signaling component is specific to mTORC2 and functions in parallel to the insulin pathway

71 The connection between mTORC2 and Mcl-1 stability has not been established and

72 eta phosphorylation and inhibition, by which mTORC2 and pAKT-S473 negatively regulate axon regenerati

73 hat hinders S473 and T308 phosphorylation by mTORC2 and PDK1.

74 ly, we detected a direct association between mTORC2 and SCF-FBXW7; this association could be inhibite

75 n suggested; however, the connection between mTORC2 and SREBP1 has not been clearly established and h

76 IRF4 expression required both mTORC2 and Stat6 pathways, providing an underlying mecha

77 eals that Sesn3 interacts with and activates mTORC2 and subsequently stimulates Akt phosphorylation a

78 y of the metabolic checkpoint kinase complex mTORC2 and the serine-threonine kinase Akt, and loss of

79 by mammalian target of rapamycin complex 2 (mTORC2) and the phosphatidylinositol 3-kinase (PI3K)/pho

80 of mammalian target of rapamycin complex 2 (mTORC2) and thereby upregulates Snail expression.

81 -like peptides, and requires PI3K, PDK, AKT, mTORC2, and activation of mTORC1 through the combined ef

82 orrelates with the activation of AKT, STAT3, mTORC2, and HIPPO signaling pathways and inactivation of

83 vant pool of PI(4,5)P2 and as a regulator of mTORC2, and show a phenomenon similar to the "butterfly

84 We report here that mTORC1 and mTORC2 are activated in response to exogenously supplied

85 We show that mTORC1 and mTORC2 are both required to enact DNA damage repair and

86 nositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTO

87 at mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and G

88 et of rapamycin (mTOR) complexes, mTORC1 and mTORC2, are master regulators of cellular survival, grow

89 an unbiased proteomic screen, we identified mTORC2 as a critical regulator of amino acid metabolism

90 f upstream kinases including PI3K, PDK1, and mTORC2 as well as closely related kinases that affect ce

91 the mammalian target of rapamycin complex 2 (mTORC2) as a key regulator of bladder cancer cell migrat

92 I3K) dependent activation of both mTORC1 and mTORC2, as measured by increased phosphorylation of S6K1

93 The negative effect of p17 on mTORC2 assembly and Akt phosphorylation at S473 is rever

94 wnregulating ribosomal proteins, p17 reduces mTORC2 assembly and disrupts mTORC2-robosome association

95 Our studies establish a PTEN-mTORC2 axis that maintains Treg cell stability and coord

96 timulated by insulin + IGF-1 was mediated by mTORC2 but did not involve mTORC1.

97 ctly binds to and suppresses the function of mTORC2 but not mTORC1.

98 we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndr

99 TORC1 or independent inhibition of mTORC1 or mTORC2 but was blocked by inhibition of mTORC1/2.

100 ted primarily from inhibition of mTORC1 (not mTORC2), but did not require new protein synthesis or ke

101 how that LanCL2 also binds to the Akt kinase mTORC2, but not phosphoinositide-dependent kinase 1.

102 Whilst interaction with PDK1 and the mTORC2 complex component SIN1 was preserved in the mutan

103 uses impaired AKT activation via compromised mTORC2 complex function.

104 n the TORC2 complex in fission yeast and the mTORC2 complex in mammals.

105 , a key regulatory/structural subunit of the mTORC2 complex, was increased in AS mice and decreased a

106 ich disrupts its interaction with the unique mTORC2 component SIN1 to favour mTORC1 formation.

107 we examine the localization of the obligate mTORC2 component, mSin1, inside cells and report the dev

108 of iTregs from naive CD4(+) T cells, and the mTORC2 component, Rictor, contained a functional target

109 A similar effect was seen when Rictor, a key mTORC2 component, was selectively silenced.

110 ed that both mTORC1 and, to a lesser extent, mTORC2 contribute to both CD4 and CD8 T-cell accumulatio

111 hat mammalian target of rapamycin complex 2 (mTORC2) contributes to BCR-mediated lytic induction and

112 Our data suggest that Rictor/mTORC2 controls an amino acid-sensitive checkpoint that

113 malian target of rapamycin (mTOR) complex 2 (mTORC2) couples extracellular growth and survival cues w

114 nistic target of rapamycin (mTOR) complex 2 (mTORC2) declines with age in the brain of both fruit fli

115 mple, INK128), which inhibit both mTORC1 and mTORC2, decreased mSREBP1 levels in various cancer cell

116 d Th17 cell-polarizing ability of endogenous mTORC2-deficient DC after TLR4 ligation in vivo.

117 elopment, is expressed at a similar level in mTORC2-deficient iNKT cells compared with that in the wi

118 te for the first time an enhanced ability of mTORC2-deficient myeloid DC to stimulate and polarize al

119 Depletion of [ATP]i inhibited mTORC2 dependent NFkappaB activation in Napa(hyh/hyh) ce

120 ced mammalian target of rapamycin complex 2 (mTORC2)-dependent phosphorylation of Akt on Ser(473) and

121 ypertrophy in the remaining kidney; however, mTORC2-dependent AKT phosphorylation did not increase fu

122 agment N2 bound the FGFR, and this inhibited mTORC2-dependent Akt Ser-473 phosphorylation and ERK2 ph

123 ctor in bladder cancer cells, could regulate mTORC2-dependent bladder cancer cell motility and invasi

124 pha-ketoglutarate, which are generated in an mTORC2-dependent manner.

125 Further, mutant PKCepsilon caused impaired mTORC2-dependent pAKT-S473 following rapamycin treatment

126 han wild-type PKCepsilon and the dynamics of mTORC2-dependent priming of mutant PKCepsilon was altere

127 mTORC1 and mTORC2 differentially control normal and leukemic stem c

128 mTORC2 downregulated the energy sensor AMP-activated pro

129 Hence, it is clear that inhibition of mTORC2 enhances Mcl-1 degradation, resulting in Mcl-1 re

130 ical) and indirect (biochemical via PLD2 and mTORC2) feedback loops in organizing cell polarity and m

131 ata unravel a vital and nonredundant role of mTORC2 for distal tubular K+ handling.

132 status of GbetaL dictates the homeostasis of mTORC2 formation and activation.

133 e GbetaL interaction with SIN1, facilitating mTORC2 formation in response to various growth signals.

134 taL(DeltaW297) truncation, leads to elevated mTORC2 formation, which facilitates tumorigenesis, in pa

135 evealing a dependence of mTORC1 signaling on mTORC2 function in activated MCs.

136 the kidney has been widely studied; however, mTORC2 function in renal tubules is poorly characterized

137 echanism between these two pathways in which mTORC2 functions as a novel and critical mediator.

138 These data suggest mTORC2 functions in WAT as part of an extra-hepatic nutr

139 t mechanistic target of rapamycin complex 2 (mTORC2) functions in white adipose tissue (WAT) to contr

140 Instead, we found that Rictor/mTORC2 has an essential role in T cell amino acid sensin

141 the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes.

142 in, we show that mTOR complex 1 (mTORC1) and mTORC2 have distinct roles in the generation of CD8+ T c

143 Thus, mTORC2 impacts development via regulation of the quantit

144 Deficiency of mTORC2 impaired CD4(+) T cell accumulation and immunoglo

145 NKT (iNKT) cell development is controlled by mTORC2 in a cell-intrinsic manner.

146 ated as a contributing upstream activator of mTORC2 in a pathway that involved PI3K and AKT.

147 roduction and determined the requirement for mTORC2 in activation of the kinase Akt.

148 Our results suggest that targeting PI3K and mTORC2 in aggressive neuroblastomas with an immature phe

149 alterations, suggesting a distinct role for mTORC2 in cancer as well.

150 the relative contributions of mTORC1 versus mTORC2 in cancer, their role in tumor-associated blood v

151 r, our findings establish a central role for mTORC2 in IFNgamma signaling and type II IFN responses.

152 Our findings define a role for mTORC2 in macrophages in integrating signals from the im

153 ctivation of the mTORC2 pathway, and loss of mTORC2 in macrophages suppressed tumor growth and decrea

154 Our findings uncover the role of mTORC2 in metabolic reprogramming and have implications

155 indings provide new insight into the role of mTORC2 in regulating DC function and may have implicatio

156 gate the role of mTOR complex 1 (mTORC1) and mTORC2 in regulating MC collagen expression, a hallmark

157 Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell s

158 Here, we generated mice lacking mTORC2 in the distal tubule (Rictorfl/fl Ksp-Cre mice),

159 ndings reveal a novel biological function of mTORC2 in the regulation of lipogenesis and warrant furt

160 egarding the functions of mTORC1 compared to mTORC2 in this regard or the respective impacts on trans

161 g the relative contribution of mTORC1 versus mTORC2 in vascular endothelial cells.

162 Ser473 residue of AKT, a selective target of mTORC2, in a SMAD2- and SMAD4-independent manner and inc

163 Thus, mTORC2 inhibition apparently induces Mcl-1 degradation t

164 Thus mTORC2 inhibition clearly facilitates GSK3-dependent, FB

165 mTORC2 inhibition resulted in metabolic reprogramming, w

166 Hence it is mTORC2 inhibition that causes mSREBP1 reduction.

167 BXW7, prevented mSREBP1 reduction induced by mTORC2 inhibition.

168 ficiency and suggests that the importance of mTORC2 inhibitor in the treatment of MFN2 downregulated

169 phoid cells after treatment with dual mTORC1/mTORC2 inhibitors.

170 could be reduced by treatment with PI3K and mTORC2 inhibitors.

171 was directly linked to an increase in SIRT1-MTORC2 interaction and RICTOR deacetylation.

172 These data indicate that mTORC2 is a critical signaling node required for VEGF-me

173 Here, we found that mTORC2 is activated by nutrient deprivation due to decre

174 Additionally, mTORC2 is essential for proper expression and nuclear ac

175 colleagues suggest activation of mTORC1 and mTORC2 is required for OIS evasion in human melanomas ha

176 malian target of rapamycin (mTOR) complex 2 (mTORC2) is a multiprotein complex that is responsible fo

177 ls, mammalian target of rapamycin complex 2 (mTORC2) is required for chemoattractant-mediated activat

178 lso known as MLST8) assemble into mTORC1 and mTORC2, it remains largely unclear what drives the dynam

179 ibited Sin1 translation, and thus suppressed mTORC2 kinase activity and invasion in colon tumor cells

180 Thus, both mTORC1 and mTORC2 kinase activity is tightly controlled in cells.

181 sassociation of mTOR/rictor and reduction of mTORC2 kinase activity.

182 e dynamic organization and activation of the mTORC2 kinase under both physiological and pathological

183 bosome association, both of which inactivate mTORC2 leading to inhibition of Akt phosphorylation at S

184 ts with Sin1 and blocks the access of Akt to mTORC2, leading to attenuated Akt activation and increas

185 Thus, mTORC2 links Akt to the distinct physiologic programs re

186 raptor (inhibits mTORC1) or rictor (inhibits mTORC2) markedly decreased basal folate uptake.

187 bited by TORKinib treatment, suggesting that mTORC2 may directly associate with and inhibit the SCF-F

188 fruit flies and rodents and that the loss of mTORC2-mediated actin polymerization contributes to age-

189 nitiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the

190 that FOXO1 is mainly phosphorylated through mTORC2-mediated phosphorylation of protein kinase B at S

191 ugh inhibiting mTORC1 and possibly enhancing mTORC2-mediated regulation of synaptic cytoskeletal elem

192 We elucidate how mTORC2 modulates a glutamine-requiring biosynthetic path

193 ding (eIF4E-binding) protein 1 (4E-BP1), and mTORC2 modulates AKT activation.

194 s part of two distinct complexes, mTORC1 and mTORC2, mTOR is the major regulator of growth (mass accu

195 ncreased mechanistic target of rapamycin C2 (mTORC2) nucleation and activity leading to tumor growth

196 We report here that the mTORC2 obligate cofactor Rictor is enriched in HER2-ampl

197 ane and counteracts the inhibitory effect of mTORC2 on CMA.

198 mTORC2 operated in parallel with the IL-4Ralpha-Stat6 pa

199 found that pharmacologically boosting either mTORC2 or actin polymerization enhances LTM.

200 to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or m

201 Genetic inhibition of mTORC2, or pharmacologic inhibition of the mammalian tar

202 ies were found to block both mTORC1(pS6) and mTORC2(pAktS473) signaling in PC-3 cancer cells, in vitr

203 more, siRNA-mediated knockdown of rictor, an mTORC2 partner protein, reduced mTORC1 substrate phospho

204 scriptional derepression of DIO2 through the mTORC2 pathway as defined in rictor knockdown cells.

205 d macrophages required the activation of the mTORC2 pathway, and loss of mTORC2 in macrophages suppre

206 Lysosomal Akt, a target of the mTORC2/PHLPP1 kinase-phosphatase pair, modulates CMA act

207 The lysosomal mTORC2/PHLPP1/Akt axis could become a target to restore

208 mTORC2 phosphorylates serine 26 at the cytosolic N termi

209 Glut1-mediated glucose uptake also requires mTORC2 phosphorylation of the HM domain, demonstrating b

210 phosphorylation of the kinase domain but not mTORC2 phosphorylation of the HM domain.

211 Additionally, mTORC1 but not mTORC2 plays an important role regulating the proliferat

212 r, an essential component of mTOR complex 2 (mTORC2), plays a pivotal role in regulating mTOR signali

213 ndicate the existence of spatially separated mTORC2 populations with distinct sensitivity to PI3K ins

214 TOR inhibitor PF-04691502 does not induce an mTORC2 positive feedback loop similar to other PI3K inhi

215 Accordingly, we conclude that mTORC2 positively regulates mSREBP1 stability and lipoge

216 The elevated mTORC2 promotes cancer cell growth and metastasis via Ak

217 Thus, mTORC2 promotes cancer via formation of lipids essential

218 Mechanistically, Rictor/mTORC2 promotes ChREBPbeta expression in part by control

219 d metabolomic analyses revealed that hepatic mTORC2 promotes de novo fatty acid and lipid synthesis,

220 cycle arrest was mediated in part by Rictor/mTORC2, providing evidence that this nutrient recognitio

221 Inhibition of PI3K/mTORC2 reduces this phosphorylation and increases the du

222 However, it is not known whether rictor and mTORC2 regulate mast cell activation.

223 arget of rapamycin complex 1 (mTORC1) and 2 (mTORC2) regulate folate transport by post-translational

224 wild-type mice, demonstrating that striatal mTORC2 regulates AMPH-stimulated behaviors.

225 indings highlight a novel mechanism by which mTORC2 regulates cell survival and growth by stabilizing

226 e in serum aldosterone levels, implying that mTORC2 regulates kaliuresis.

227 Activation of mTORC2 regulates the phosphorylation of the Smad2/3-T220

228 mTOR complex 2 (mTORC2) regulates cell survival and growth through undef

229 wever, whether sestrins are also involved in mTORC2 regulation and function is unclear.

230 y both nutrients and growth factors, whereas mTORC2 responds primarily to extracellular cues such as

231 s amino acid abundance to promote anabolism, mTORC2 responds to declining glutamine catabolites in or

232 lar Cell, Moloughney et al. (2016) find that mTORC2 responds to falling levels of glucose and glutami

233 a positive feedback loop via mTOR complex 2 (mTORC2), resulting in activation of prosurvival signalin

234 L2 family member PUMA, whereas inhibition of mTORC2 results in nuclear factor-kappaB-mediated express

235 ns, p17 reduces mTORC2 assembly and disrupts mTORC2-robosome association, both of which inactivate mT

236 r (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (S

237 Examining the components of mTORC2 showed that Pdcd4 knockdown increased the protein

238 Blockage of the mTORC2 signal pathway prevented cytokine-induced phospho

239 (Homozygous) mice showed reduced mTORC1 and mTORC2 signaling along with transcripts and protein leve

240 te deficiency inhibited placental mTORC1 and mTORC2 signaling and decreased trophoblast plasma membra

241 n in MCs increases PI3K dependent mTORC1 and mTORC2 signaling and leads to increased collagen I expre

242 Our findings implicate mTORC2 signaling as a novel pathway regulating striatal

243 In mice deficient in mTORC2 signaling because of the conditional deletion of

244 Therefore, the AKT/WHSC1/mTORC2 signaling cascade represents a vicious feedback l

245 a negative regulator shared across STAT3 and mTORC2 signaling cascades, functioning as a tumor suppre

246 together, our findings establish that Rictor/mTORC2 signaling drives Akt-dependent tumor progression

247 and underscore the need to further delineate mTORC2 signaling in activated cell states.

248 We demonstrate that mice with disrupted mTORC2 signaling in brain exhibit altered striatal DA-de

249 f specific functional readouts of mTORC1 and mTORC2 signaling in multiple maternal and fetal tissues.

250 turn inhibits rictor, resulting in decreased mTORC2 signaling in Purkinje neurons of AS mice.

251 Islets with reduced mTORC2 signaling in their beta-cells (RIPCre;Rictor(fl/f

252 ive crosstalk that occurs between mTORC1 and mTORC2 signaling pathways, we assessed the role of the m

253 Functionally, iNKT cells devoid of mTORC2 signaling showed reduced number of IL-4-expressin

254 ulates intestinal fat metabolism by engaging mTORC2 signaling to promote the intertissue transport of

255 In contrast, mTORC2 signaling was enhanced in Tsc1 (tg) mice.

256 t PI3K/Akt signaling may positively regulate mTORC2 signaling, likely through suppressing GSK3-depend

257 can induce bladder cancer cell invasion via mTORC2 signaling, which may be applicable in most bladde

258 ed, suggesting enhanced mTORC1 but inhibited mTORC2 signaling.

259 t of Akt or mTORC1 signaling but relied upon mTORC2 signaling.

260 r performance but also normalized mTORC1 and mTORC2 signaling.

261 and mammalian target of rapamycin complex-2 (mTORC2) signaling.

262 ositively correlated to placental mTORC1 and mTORC2 signalling activity in human pregnancy.

263 Abrogation of mTORC2 signalling in macrophages by selective conditiona

264 Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages.

265 Inhibition of mTORC2 significantly suppresses MFN2 deficient tumor gro

266 mTORC1 or mTORC2 silencing markedly decreased the plasma membrane

267 By viral gene delivery, we downregulated mTORC2 solely in the dorsal striatum of adult wild-type

268 of human cancers harboring amplifications in mTORC2-specific genes as the only actionable genomic alt

269 al mTORC1/2 kinase inhibitors and developing mTORC2-specific inhibitors for use in this setting.

270 Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC end

271 In particular, mTORC2 stimulated sphingolipid (glucosylceramide) and gl

272 1 and 4E-BP1 (mTORC1 substrates) and AKT (an mTORC2 substrate).

273 K1) and S6 was elevated, whereas that of the mTORC2 substrates AKT and N-myc downstream regulated 1 w

274 firmed by increased phosphorylation of other mTORC2 substrates.

275 Conditionally deleting the essential mTORC2 subunit Rictor in mature adipocytes decreases ChR

276 3K/AKT/mTORC signalling, specifically of the mTORC2 subunit, in the different naive hESCs.

277 using CDK4/6 inhibitors releases Rb-mediated mTORC2 suppression.

278 iciency of Rictor, an essential component of mTORC2, survive despite a hypoplastic epidermis and disr

279 hout a compensatory activation of the rictor/mTORC2 target Akt (S475).

280 results define specific roles for mTORC1 and mTORC2 that link metabolism and CD8+ T cell effector and

281 As an obligatory component of mTORC2, the role of Rictor in T cells is well establishe

282 hanistic studies reveal that MFN2 suppresses mTORC2 through direct interaction by binding its domain

283 imulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and glucose

284 ings suggest that Sesn3 can activate Akt via mTORC2 to regulate hepatic insulin sensitivity and gluco

285 the mammalian target of rapamycin complex 2 (mTORC2) to limit actin nucleation.

286 CTOR, a pivotal component of mTOR complex 2 (mTORC2), to further enhance AKT activity.

287 et how growth factors target the activity of mTORC2 toward Akt is unknown.

288 cyclin-dependent kinase 2 (Cdk2)/cyclin A or mTORC2, under distinct physiological conditions, promote

289 endogenous transmembrane protein upstream-of-mTORC2 (UT2) negatively regulates activation of STAT3.

290 somal pool, the activity and localization of mTORC2 via the Sin1 pleckstrin homology domain at the pl

291 specific ablation of Raptor/mTORC1 or Rictor/mTORC2, we revealed that both mTORC1 and, to a lesser ex

292 tinct pathways driven by PI3Kalpha/delta and mTORC2, whereas in activated HSCs, RAS signaling shifts

293 of mammalian target of rapamycin complex 2 (mTORC2), which was confirmed by increased phosphorylatio

294 function was more dependent on PDK1 than on mTORC2, which indicates that PDK1 plays a dominant role

295 otein, lipid, and ribosome biosynthesis, and mTORC2, which regulates cytoskeleton functions.

296 ct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), whose activities and substrate specificities ar

297 ctions in two distinct complexes, mTORC1 and mTORC2, whose activities and substrate specificities are

298 of HIV genes, consistent with inhibition of mTORC2, whose activity is critical for phosphorylation o

299 t and selective dual inhibitor of mTORC1 and mTORC2 with physicochemical and pharmacokinetic properti

300 e maturation and function of islets, whereas mTORC2 (with adaptor protein Rictor) impacts islet mass