ライフサイエンスコーパス: mTORC2

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

2 exes, mTOR Complex 1 (mTORC1) and Complex 2 (mTORC2).

3 ing mammalian target of rapamycin complex 2 (mTORC2).

4 t of two multi-subunit complexes, mTORC1 and mTORC2.

5 n activates both mTOR complex 1 (mTORC1) and mTORC2.

6 nputs as part of mTOR complex 1 (mTORC1) and mTORC2.

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

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

9 h stabilizes both mTOR complexes: mTORC1 and mTORC2.

10 ase forms two distinct complexes: mTORC1 and mTORC2.

11 hrough two multiprotein complexes, mTORC1 or mTORC2.

12 ls, with subsequent activation of mTORC1 and mTORC2.

13 hosphorylation at T308 via PI3K and S473 via mTORC2.

14 y assembling a supercomplex with Ras-GTP and mTORC2.

15 otent selective dual inhibitor of mTORC1 and mTORC2 (29b).

16 nistic target of rapamycin (mTOR) complex 2 (mTORC2), a protein kinase that phosphorylates and activa

17 These data suggest that a principal mTORC2 action is controlling nuclear-cytoplasmic acetyl-

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

19 OD mimic MnTnBuOE-2-PyP(5+) (MnP) attenuates mTORC2 activation and suppresses UVB-induced mitophagy.

20 port for a model that links TCR signaling to mTORC2 activation via phosphoinositide 3-kinase signalin

21 TORca or mTORkd affected only mTORC1 but not mTORC2 activities, with corresponding changes in the act

22 lated mTORC2 components directly to increase mTORC2 activity and downstream signaling.

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

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

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

26 ining component Rictor specifically inhibits mTORC2 activity and reverses the behavioral and neurophy

27 elay of barrier formation in which epidermal mTORC2 activity controls FLG processing and de novo epid

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

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

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

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

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

33 gulation by growth factors of the endogenous mTORC2 activity.

34 Ser(474) phosphorylation without perturbing mTORC2 activity.

35 2 cofactors RICTOR and SIN1, thus abrogating mTORC2 activity.

36 nce in mature brown adipocytes also suggests mTORC2 acts through ACLY to increase carbohydrate respon

37 Specific deletion of the mTORC2 adaptor gene Rictor in Foxp3-deficient T(reg) cel

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

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

40 MTORC2-AKT is a key regulator of carbohydrate metabolism

41 ng a previously unappreciated selectivity in mTORC2-AKT signaling.

42 roteins are inactive, our study reveals that mTORC2-AKT signalling is activated by Rho-GDP.

43 ectively, our study reveals a novel role for mTORC2-Akt(S473)-FoxO1-T-bet axis in suppressing the tra

44 These results not only uncover a caspase-2-mTORC2-Akt-GSK3beta signaling pathway, but also suggest

45 we show that leptin induction activates the mTORC2/Akt pathway and subsequently down-regulates Phlpp

46 s glycemic control through the hepatic Sirt1/mTORC2/Akt pathway, whereas it increases fatty acid oxid

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

48 high-fat diet (HFD) inhibited hepatic Sirt1/mTORC2/Akt signaling, and the inhibition was reversed by

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

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

51 ents suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establi

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

53 Regulation of Cav-1 activity by mTORC2 also alters the abundance of caveolae, which are

54 iments demonstrate the existence of pools of mTORC2 and AKT that are sensitive to lysosome positionin

55 ys reactivation of not only mTORC1, but also mTORC2 and AKT upon serum replenishment.

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

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

58 ms the distinct protein complexes mTORC1 and mTORC2 and integrates signals from the environment to co

59 mTORC2 and its substrate kinase AKT have a widespread di

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

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

62 SIRT6 is the FoxO1 deacetylase suppressed by mTORC2 and show an endogenous interaction between SIRT6

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

64 1 mediates CaSR-dependent AKT activation via mTORC2 and thereby stabilizes beta-catenin in osteoblast

65 f mechanistic target of rapamycin complex 2 (mTORC2) and suppressed insulin-induced Akt phosphorylati

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

67 the rapamycin-insensitive complex-2 of mTOR (mTORC2), and genes involved in axon growth, whereas gene

68 Functionally, inactivation of AMPK, mTORC2, and Akt increased apoptosis during acute energet

69 t acts in two distinct complexes, mTORC1 and mTORC2, and is dysregulated in many diseases including c

70 MAD2 or SMAD3 as well as inhibition of PI3K, mTORC2, and PDGFR abrogated the induction of GLS1 by TGF

71 mTORC2 appears dispensable for most other AKT actions ex

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

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

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

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

76 functional Ras-associated proteins, defined mTORC2 as a new direct Ras effector, and offers a strate

77 haviors in a Pten mutant model, highlighting mTORC2 as a potential therapeutic target in mTORopathies

78 Collectively, these data unveil mTORC2 as a target of AMPK and the AMPK-mTORC2 axis as a

79 We confirmed the inhibition of mTORC1/mTORC2 as the underpinning mechanism for macropinocytosi

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

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

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

83 rresponding mutation on mTOR interfered with mTORC2 assembly and activity without affecting mTORC1.

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

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

86 veil mTORC2 as a target of AMPK and the AMPK-mTORC2 axis as a promoter of cell survival during energe

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

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

89 unexpectedly found that genetic deletion of mTORC2 (but not mTORC1) activity prolonged lifespan, sup

90 ST8 is critical for assembly and activity of mTORC2, but not mTORC1, an observation that could enable

91 ge in vitro kinase assay, phosphorylation of mTORC2 by recombinant AMPK was sufficient to increase mT

92 recombinant AMPK was sufficient to increase mTORC2 catalytic activity toward Akt.

93 n mLST8 and the NH(2)-terminal domain of the mTORC2 cofactor SIN1.

94 er, mLST8 loss blocked mTOR association with mTORC2 cofactors RICTOR and SIN1, thus abrogating mTORC2

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

96 uses impaired AKT activation via compromised mTORC2 complex function.

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

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

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

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

101 ase-2 degrades Rictor, a key mTOR complex 2 (mTORC2) component, to inhibit Akt activation, which lead

102 Hence, AMPK phosphorylated mTORC2 components directly to increase mTORC2 activity a

103 genic Ras directly bound two mTOR complex 2 (mTORC2) components, mTOR and MAPKAP1, to promote mTORC2

104 protein translation, and autophagy, whereas mTORC2 contributes to actin dynamics.

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

106 mTORC2 controls glucose and lipid metabolism, but the me

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

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

109 Inhibition of mTORC1, but not mTORC2, decreased protein expression of ETC complexes I-

110 Restoration of Akt-Ser473 phosphorylation in mTORC2-deficient keratinocytes through expression of con

111 arning classifiers revealed that half of the mTORC2-deficient NK cells belongs to the least mature NK

112 Importantly, PI3K/Akt inhibition by Rictor/mTORC2 deletion blocks distant dispersal, restricting gl

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

114 d mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, T cell proliferat

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

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

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

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

119 AMPK-mediated activation of mTORC2 did not result from AMPK-mediated suppression of

120 nd replenishment, suggesting that mTORC1 and mTORC2 differentially modulate postsynaptic responsivene

121 al. now report that AMPK directly activates mTORC2 during energetic stress to enhance cell survival.

122 mTORC2 enabled the Ras pro-proliferative cell cycle tran

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

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

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

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

127 Our findings suggest a new paradigm of mTORC2 function filling an important gap in our understa

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

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

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

131 in promoting RBC development, we showed that mTORC2 has an opposing role, as Rictor-deficient progeni

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

133 functionally distinct complexes, mTORC1 and mTORC2, has been implicated in several neurological diso

134 sphorylation by ablating its upstream kinase mTORC2, have implicated Ser(474) phosphorylation as a dr

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

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

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

138 mall G protein Rho GTPase directly activates mTORC2 in AKT phosphorylation in social amoebae (Dictyos

139 an endogenous interaction between SIRT6 and mTORC2 in both mouse and human cells.

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

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

142 ission, we genetically inactivated mTORC1 or mTORC2 in cultured mouse glutamatergic hippocampal neuro

143 and suppresses graft rejection, the role of mTORC2 in DCs in determining host responses to transplan

144 ing a sex hormone-dependent role for hepatic mTORC2 in female longevity, our results demonstrate that

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

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

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

148 n (Rictor), encoding an essential subunit of mTORC2 in mouse epidermis (epidermis-specific homozygous

149 e utilization studies additionally implicate mTORC2 in promoting acetyl-CoA synthesis from acetate th

150 These data indicate a role of mTORC2 in regulating tumor growth by macropinocytosis an

151 These findings suggest that mTORC2 in skin DCs restrains effector CD8(+) T cell resp

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

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

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

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

156 the influence of mTOR inhibitors that target mTORC2 in transplant.

157 Thus mTORC2 inhibition clearly facilitates GSK3-dependent, FB

158 PI3K suppression by mTORC2 inhibition synergized with dasatinib and abolishe

159 Hence it is mTORC2 inhibition that causes mSREBP1 reduction.

160 silenced raptor (mTORC1 inhibition), rictor (mTORC2 inhibition) or DEPTOR (mTORC1/2 activation) in cu

161 BXW7, prevented mSREBP1 reduction induced by mTORC2 inhibition.

162 cy and safety of a novel low-toxicity mTORC1/mTORC2 inhibitor (MTI-31) as a treatment for glioma when

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

164 Here we demonstrate that dual mTORC1/mTORC2 inhibitors OSI-027 and PP242 cause catastrophic m

165 at mLST8 functions as a scaffold to maintain mTORC2 integrity and kinase activity, unveiling a new av

166 nscriptional program, and perturbing the Ras-mTORC2 interaction impaired Ras-dependent neoplasia in v

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

168 mTORC2 is activated in TMEM127-deficient hepatocytes sug

169 t the sex-specific impact of reduced hepatic mTORC2 is not reversed by depletion of sex hormones.

170 Collectively, our findings indicate that mTORC2 is the major driver underlying the neuropathophys

171 mTOR complex 2 (mTORC2) is a major regulator of bladder cancer cell migr

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

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

174 C2) components, mTOR and MAPKAP1, to promote mTORC2 kinase activity at the plasma membrane.

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

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

177 posure to rapamycin, an mTORC1 inhibitor, or mTORC2 knockdown alone had little or reduced effect rela

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

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

180 wnstream AKT signaling appears unaffected by mTORC2 loss.

181 Furthermore, Rho-GDP rescues defects in both mTORC2-mediated AKT phosphorylation and directed cell mi

182 e to biology and medicine, it is unclear how mTORC2-mediated AKT phosphorylation is controlled.

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

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

185 Our results demonstrate a unique role for mTORC2-mediated regulation of caveolae formation in acti

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

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

188 males, perhaps because inhibition of hepatic mTORC2 (mTOR Complex 2) specifically reduces the lifespa

189 associated with and directly phosphorylated mTORC2 (mTOR in complex with rictor).

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

191 al., 2019) demonstrates that suppression of mTORC2, not mTORC1, ameliorates survival, seizures, and

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

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

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

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

196 h depletion of Rictor, the unique subunit of mTORC2, or the mTOR kinase itself also inhibits the vira

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

198 rotein expression via activation of the AMPK/mTORC2 pathway, which controls cellular energy status.

199 entify AGR2 as an interacting partner of the mTORC2 pathway.

200 the mammalian target of the mTOR complex 2 (mTORC2) pathway.

201 ghlight a link between leptin signaling, the mTORC2/Phlpp1/Akt axis, and lysosomal activity in macrop

202 ics dual approach was used to identify novel mTORC2 phosphoprotein targets in actively invading cance

203 mTORC2 phosphorylates AKT in a hydrophobic motif site th

204 mTORC2 phosphorylates serine 26 at the cytosolic N termi

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

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

207 apamycin had reduced Akt1 and mTORC1 but not mTORC2 phosphorylation.

208 ves a multimodal signaling network involving mTORC2-PKCzeta-mediated activation of the calcium-depend

209 mTORC2 plays critical roles in metabolism, cell survival

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

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

212 Thus, mTORC2 promotes cancer via formation of lipids essential

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

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

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

216 get of rapamycin (mTOR) complex (mTORC)1 and mTORC2 regulate the differentiation and function of immu

217 Functional testing shows that mTORC2 regulates Cav-1 localization and dynamic phosphor

218 In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however t

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

220 Since mTORC2 regulates the expression of T-bet through Akt(S47

221 on and invasion, but the mechanisms by which mTORC2 regulates these processes are unclear.

222 mTOR) functions as two complexes (mTORC1 and mTORC2), regulating cell growth and metabolism.

223 Lipolysis is increased due to mTORC2 repression, increasing fatty acids to support cel

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

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

226 Mechanistically, loss of mTORC2 results in an increased expression of signature g

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

228 h components of the mTOR pathway (mTORC1 and mTORC2) reveal a mechanism of FLCN function during exit

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

230 an antisense oligonucleotide (ASO) targeting mTORC2's defining component Rictor specifically inhibits

231 an observation that could enable therapeutic mTORC2-selective inhibition as a therapeutic strategy.

232 ify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes.

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

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

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

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

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

238 eregulate homeostatic anti-inflammatory BVRA/mTORC2 signaling and thereby contribute to chronic infla

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

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

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

242 s drug metformin (GlucoPhage) also increased mTORC2 signaling in liver in vivo and in primary hepatoc

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

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

245 However, S Typhimurium-induced mTORC2 signaling led to phosphorylation of Akt at S473,

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

247 ly regulates filamentous actin (F-actin) and mTORC2 signaling to achieve equipoise in immune response

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

249 Epidermal mTORC2 signaling was specifically disrupted by deleting

250 is positively controlled by mTORC1-S6K1 and mTORC2 signaling.

251 depend upon mitochondrial dynamics and ICOS-mTORC2 signaling.

252 malian target of rapamycin (mTOR) complex 2 (mTORC2) signaling and gives rise to augmented aerobic gl

253 of AMPK activators increased mTOR complex 2 (mTORC2) signaling in an AMPK-dependent manner in culture

254 of mammalian target of rapamycin complex 2 (mTORC2) signaling in epidermal barrier formation.

255 d mechanistic target of rapamycin complex 2 (mTORC2) signaling, leading to clinical trials for NF2 an

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

257 Abrogation of mTORC2 signalling in macrophages by selective conditiona

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

259 depletion not only activated both mTORC1 and mTORC2 signals to promote cell proliferation and surviva

260 morigenesis via the activation of mTORC1 and mTORC2 signals.

261 Inhibition of mTORC2 significantly suppresses MFN2 deficient tumor gro

262 life survival of female mice lacking hepatic mTORC2, significantly increasing the survival of those m

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

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

265 y, unveiling a new avenue for development of mTORC2-specific inhibitors.

266 mTORC1 and mTORC2-specific serum/glucocorticoid-regulated kinase 1

267 leukocytes and triggered phosphorylation of mTORC2-specific targets, including Akt, PKCzeta, AMPKalp

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

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

270 1 and 4E-BP1 (mTORC1 substrates) and AKT (an mTORC2 substrate).

271 AKT kinases are the canonical mTORC2 substrates; however, deleting Rictor in brown adi

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

273 ow that conditionally deleting the essential mTORC2 subunit Rictor in murine brown adipocytes inhibit

274 3K/AKT/mTORC signalling, specifically of the mTORC2 subunit, in the different naive hESCs.

275 kinase operates in two complexes, mTORC1 and mTORC2, suggesting that mTOR's role in synaptic transmis

276 mTORC2 targets included focal adhesion kinase, proto-onc

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

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

279 Growth factors activate mTOR complex 2 (mTORC2) through poorly defined mechanisms to modulate ce

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

281 By showing that AMPK activates mTORC2 to increase cell survival, these data provide a p

282 It also activated mTORC2 to phosphorylate AKT at serine 473 for full activ

283 strong TCR signal were required to activate mTORC2 to phosphorylate Ser-473 on AKT.

284 ion results in activation of both mTORC1 and mTORC2 to promote virus replication.

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

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

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

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

289 delayed-type hypersensitivity model in which mTORC2 was absent in cutaneous DCs.

290 Using a mouse model in which mTORC2 was deleted specifically in CD11c(+) DCs (TORC2(D

291 eEPSCs were postsynaptic and the effects of mTORC2 were presynaptic.

292 but insufficient to activate mTOR complex 2 (mTORC2), whereas elevated PIP3 levels generated by a str

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

294 ulti-protein signaling complexes, mTORC1 and mTORC2, which are master regulators of cell growth, meta

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

296 n requires the activation of both mTORC1 and mTORC2, which negatively regulates autophagy to facilita

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

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

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

300 ST8 is a shared component of both mTORC1 and mTORC2, yet little is known regarding how mLST8 contribu