Gene interactions and pathways from curated databases and text-mining

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AKT1 — RICTOR

Pathways - manually collected, often from reviews:

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Sarbassov et al., Mol Cell 2006 : mTORC2 phosphorylates and activates Akt/PKB , a key regulator of cell survival ... mTORC2 phosphorylates and activates Akt/PKB , a key regulator of cell survival
Zeng et al., Blood 2007 (Leukemia, Myeloid, Acute) : Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML
Hietakangas et al., Genes Dev 2007 : Here we analyze the role of TORC2 mediated AKT phosphorylation in Drosophila
Woo et al., J Biol Chem 2007 (Breast Neoplasms...) : Despite no significant effect of PRR5 on mTORC2 mediated Akt phosphorylation, PRR5 silencing inhibits Akt and S6K1 phosphorylation and reduces cell proliferation rates, a result consistent with PRR5 roles in cell growth and tumorigenesis
Masri et al., Cancer Res 2007 (Brain Neoplasms...) : mTORC2 has recently been shown to phosphorylate and activate Akt
McDonald et al., Cancer Res 2008 (Breast Neoplasms...) : Rictor and integrin linked kinase interact and regulate Akt phosphorylation and cancer cell survival
Wang et al., Oncology 2007 (Disease Models, Animal...) : Either siRNA Raptor or siRNA Rictor suppressed TNF-alpha expression, but the latter suppressed the effects of GM3 on TNF-alpha expression and Akt phosphorylation at Ser ( 473 ), indicating the GM3 signal to be transduced via Rictor/mTOR and Akt ( Ser ( 473 ) ), leading to TNF-alpha stimulation
Hietakangas et al., BMC cancer 2008 (Breast Neoplasms...) : TOR complex 2 (TORC2) activates AKT by phosphorylating it on the ` hydrophobic motif ' site
Bentzinger et al., Cell Metab 2008 (Muscular Dystrophies) : Finally, we show that activation of PKB/Akt does not require mTORC2 ... Finally, we show that activation of PKB/Akt does not require mTORC2
Werzowa et al., Br J Dermatol 2009 (Melanoma...) : Inhibition of mTORC2 led to reduced levels of phosphorylated AKT
Balasubramanian et al., Cardiovasc Hematol Agents Med Chem 2009 (Cardiomegaly) : mTORC2 regulates the actin cytoskeleton in addition to activating Akt ( Protein kinase B ) for the subsequent removal of proapoptotic factors via the UPS for cell survival
Lodeiro et al., PloS one 2009 : This beta-arrestin scaffolded complex leads to full activation of Akt through PDK1 and mTORC2 , which are not associated to the complex
Wang et al., Science signaling 2009 (Cardiovascular Diseases...) : Rapamycin treatment of diet induced obese mice or of transgenic mice with long-term activation of endothelial Akt inhibits activation of mammalian target of rapamycin (mTOR)-rictor complex 2 and Akt, prevents vascular senescence without altering body weight, and reduces the severity of limb necrosis and ischemic stroke
Bozulic et al., Curr Opin Cell Biol 2009 (Neoplasms) : This present review concerns PKB regulation by mTORC2 and DNA-PK in a stimulus dependent and context dependent manner and the possible implications of this for PKB activity, substrate specificity and therapeutic intervention
Breuleux et al., Mol Cancer Ther 2009 (Neoplasms) : Rictor may also play a role because rictor kinase complexes ( including mTOR/rictor ) regulate AKT S473 phosphorylation
Dibble et al., Mol Cell Biol 2009 : Although this phosphorylation event does not affect mTORC2 integrity or in vitro kinase activity, expression of a phosphorylation site mutant of Rictor ( T1135A ) in either wild-type or Rictor null cells causes an increase in the mTORC2 dependent phosphorylation of Akt on S473
Julien et al., Mol Cell Biol 2010 : While mTOR complex 1 (mTORC1) regulates mRNA translation and ribosome biogenesis, mTORC2 plays an important role in the phosphorylation and subsequent activation of Akt ... However, cells expressing a Rictor T1135A mutant were found to have increased mTORC2 dependent phosphorylation of Akt ... In addition, phosphorylation of the Akt substrates FoxO1/3a and glycogen synthase kinase 3 alpha/beta ( GSK3 alpha/beta ) was found to be increased in these cells, indicating that S6K1 mediated phosphorylation of Rictor inhibits mTORC2 and Akt signaling
Yu et al., Cancer Res 2010 (Neoplasms) : Importantly, consistent with genetic ablation of mTORC2, WYE-132 targeted P-AKT ( S473 ) and AKT function without significantly reducing the steady-state level of the PI3K/PDK1 activity biomarker P-AKT ( T308 ), highlighting a prominent and direct regulation of AKT by mTORC2 in cancer cells
Yang et al., Cell cycle (Georgetown, Tex.) 2010 (Neoplasms) : Akt activity is well-known regulated through its phosphorylation at T308 and S473 by PDK1 and mTOrC2 , respectively
Liao et al., J Cell Sci 2010 : Chemotactic activation of Dictyostelium AGC-family kinases AKT and PKBR1 requires separate but coordinated functions of PDK1 and TORC2
Wu et al., Urol Oncol 2012 (Carcinoma, Transitional Cell...) : Rictor dependent AKT activation and inhibition of urothelial carcinoma by rapamycin
Sini et al., Autophagy 2010 (Neoplasms) : mTORC2 activates AKT directly by phosphorylating Serine 473
Chen et al., Mol Carcinog 2010 (Neoplasms) : 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 ... 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
Cleveland-Donovan et al., Endocrinology 2010 (Obesity) : The mammalian target of rapamycin (mTOR)-Rictor complex regulates phosphorylation of AKT-serine ( 473 ) in 3T3-L1 adipocytes, but knockdown of Rictor by lentivirus delivered short hairpin RNA in sc preadipocytes did not affect AKT-serine ( 473 ) phosphorylation by IGF-I
Lee et al., Immunity 2010 : mTORC2 promoted phosphorylation of protein kinase B ( PKB, or Akt ) and PKC, Akt activity, and nuclear NF-kappaB transcription factors in response to T cell activation
Kim et al., J Lipid Res 2010 : The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK dependent CREB/TORC2 activation
Lee et al., Genes Dev 2010 : Collectively, these findings establish mTOR/rictor mediated Akt activation as a key driver of NSC proliferation and gliogenesis, and identify a unique mechanism for conferring brain region-specific responses to cancer causing genetic changes
Yamada et al., Histochem Cell Biol 2010 : Silencing by Rictor siRNA resulted in the attenuation of Akt phosphorylation on Ser473 and PKCa/ßII phosphorylation, as well as the inhibition of Rictor itself, suggesting that Rictor is an upstream regulator of both Akt and PKC ... Taken together, our results show that Rictor associated with mTOR ( mTORC2 ) regulates the activity of both Akt and PKC that are involved in cell functions such as NBT reduction and esterase activity induced by leukemia cell differentiation
Dunaway et al., Mol Cell Biol 2011 : Slit2 stimulates angiogenesis through mTORC2 dependent activation of Akt and Rac GTPase, the activities of which are inhibited in the presence of ephrin-A1
Murata et al., J Biol Chem 2011 (Neuroblastoma...) : A new cytosolic pathway from a Parkinson disease associated kinase, BRPK/PINK1 : activation of AKT via mTORC2
Harston et al., Am J Physiol Heart Circ Physiol 2011 (Hypertrophy) : Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes : mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and mTORC2 that activates Akt to promote cell survival
Pearce et al., Biochem J 2011 : Both complexes phosphorylate the hydrophobic motifs of AGC kinase family members : mTORC1 phosphorylates S6K ( S6 kinase ), whereas mTORC2 regulates phosphorylation of Akt , PKCa ( protein kinase Ca ) and SGK1 ( serum- and glucocorticoid induced protein kinase 1 )
Guo et al., Arterioscler Thromb Vasc Biol 2011 : According to Western blot analysis and immunoprecipitation results, rHDL promoted mTOR phosphorylation, mTOR-rictor complex formation, and mTOR-rictor dependent Akt activation, which were accompanied by increased nuclear translocation of human telomerase reverse transcriptase and enhanced nuclear telomerase activity
Hiraoka et al., Oncogene 2011 : A well conserved threonine in the turn motif ( TM ) is also constitutively phosphorylated by mTORC2 and contributes to the stability of Akt
Moore et al., J Biol Chem 2011 (MAP Kinase Signaling System) : In this study, we investigated the role of the mammalian target of rapamycin complex ( mTORC)-2 in Akt regulation using the recently identified small molecule ATP competitive mTOR inhibitors PP242 and Torin1
Lazorchak et al., Protein & cell 2011 (Cell Transformation, Neoplastic) : We also propose a novel strategy to treat cancers based on our recent discovery that mTORC2 regulates Akt protein stability
Boulbés et al., Biochem Biophys Res Commun 2011 : Based on our study we suggest that the mTORC2 dependent phosphorylation of Akt on Ser-473 takes place on the surface of ER
Hwang et al., BMB Rep 2011 (Ischemia) : The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt
Gupta et al., Blood 2012 (Lymphoma) : Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma dependent apoptosis in lymphoid malignancies
Koh et al., Endocr Relat Cancer 2012 (Carcinoma...) : Cells treated with everolimus demonstrated activation of Akt and Ret via TORC2 complex dependent and TORC2 complex independent mechanisms respectively
Fang et al., J Biol Chem 2012 (Prostatic Neoplasms) : Significantly, androgen increased TORC2 mediated AKT S473 phosphorylation without affecting the PDK1 mediated AKT T308 phosphorylation or TORC1 activity ... This study reveals a pathway linking AR to a selective activation of TORC2 , the subsequent activation of AKT , and phosphorylation of a discrete set of AKT substrates that regulate cellular proliferation and survival
Rodrik-Outmezguine et al., Cancer Discov 2011 : mTOR kinase inhibitors block mTORC1 and mTORC2 and thus do not cause the mTORC2 activation of AKT observed with rapamycin ... Inhibition of mTORC2 leads to AKT serine 473 ( S473 ) dephosphorylation and a rapid but transient inhibition of AKT T308 phosphorylation and AKT signaling
Espona-Fiedler et al., Biochem Pharmacol 2012 (Melanoma) : The inhibition of mTORC1 and mTORC2 complexes by PG or OBX resulted in a loss of AKT phosphorylation at S473, preventing its full activation, with no significant effect on T308
Misra et al., J Cell Biochem 2012 (Prostatic Neoplasms) : We measured mTORC2 dependent Akt phosphorylation at S473 in immunoprecipitates of mTOR or Rictor from 1-LN cells ... Silencing Rictor gene expression by RNAi significantly suppressed 8-CPT-2Me-cAMP induced phosphorylation of Akt at Ser ( 473 ) ... These studies represent the first report that Epac1 mediates mTORC2 dependent phosphorylation of Akt ( S473 )
Rosel et al., J Cell Sci 2012 : TORC1 is required for growth in response to growth factors, nutrients and the cellular energy state ; TORC2 regulates AKT signaling, which can modulate cytoskeletal polarization
Riaz et al., PloS one 2012 : Receptor-specific mechanisms regulate phosphorylation of AKT at Ser473 : role of RICTOR in ß1 integrin mediated cell survival ... RICTOR-mTOR was required also for LPA induced AKT Ser473 phosphorylation in MCF7 cells, but, interestingly, not in HeLa cells
Wang et al., Mol Cell Biol 2012 (Dermatitis, Seborrheic) : Surprisingly, however, TORC2 does not regulate cell growth via its best characterized target, AKT
Kaur et al., Proc Natl Acad Sci U S A 2012 : We provide evidence that mTORC2 complexes control IFN induced phosphorylation of AKT on serine 473 and their function is ultimately required for IFN dependent gene transcription via interferon stimulated response elements
Chang et al., Eur J Immunol 2012 : Sin1 deficiency blocks the mTORC2 dependent Akt phosphorylation in T cells during development and activation
Floc'h et al., Cancer Res 2012 (Disease Models, Animal...) : In human prostate cancer cell lines, although not in the mouse model, the synergistic actions of MK-2206 and ridaforolimus ( MK-8669 ) are due in part to limiting the mTORC2 feedback activation of Akt
Najafov et al., Biochem J 2012 (Neoplasms) : Akt is activated by phosphorylation of its T-loop residue ( Thr ( 308 ) ) by PDK1 ( 3-phosphoinositide dependent kinase-1 ) and its C-terminal hydrophobic motif ( Ser ( 473 ) ) by mTORC2 [ mTOR ( mammalian target of rapamycin ) complex 2 ]
Matheny et al., Growth Factors 2012 : Enhanced Akt phosphorylation and myogenic differentiation in PI3K p110ß-deficient myoblasts is mediated by PI3K p110a and mTORC2
Parrales et al., Cell Signal 2013 : Since Akt functions as an upstream activator of mechanistic target of rapamycin complex 1 ( mTORC1 ) and is also a downstream target for mTORC2 , the aim of this work was to determine whether mTOR is involved in thrombin induced RPE cell proliferation by regulating cyclin D1 expression in immortalized rat RPE-J cell line
Yao et al., Science signaling 2013 : BSTA promotes mTORC2 mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation ... The mammalian target of rapamycin complex 2 ( mTORC2 ) facilitated the phosphorylation of BSTA and its association with Akt1, and the BSTA-Akt1 interaction promoted the association of mTORC2 with Akt1 and phosphorylation of Akt1 at Ser473 in response to growth factor stimulation
Razmara et al., Cell communication and signaling : CCS 2013 : Platelet derived growth factor induced Akt phosphorylation requires mTOR/Rictor and phospholipase C-?1, whereas S6 phosphorylation depends on mTOR/Raptor and phospholipase D ... mTORC1 is activated in a PLD dependent manner and promotes phosphorylation of the S6 protein, whereas mTORC2 , in concert with PLC? signaling, promotes Akt phosphorylation
Shortt et al., Blood 2013 (Lymphoma, B-Cell) : Moreover, apoptosis was initiated at drug concentrations insufficient to antagonize PI3K/mTORC2 regulated AKT phosphorylation
Wolin et al., Cancer Lett 2013 (Neuroendocrine Tumors...) : The mTOR inhibitor everolimus has been approved by the FDA for the treatment of pNET, but its efficacy may be limited by its inability to prevent mTORC2 mediated activation of Akt
Riaz et al., J Biol Chem 2013 : Protein suppression using specific siRNAs revealed that heparanase induced phosphorylation of AKT at Ser-473 was RICTOR-mTOR dependent , whereas ILK and PAK1/2 were dispensable
Moschella et al., Cell Signal 2013 : Since mTORC2 is known to mediate the activation of a prosurvival kinase, Akt, we analyzed whether mTORC2 directly mediates Akt activation or whether it requires the participation of another prosurvival kinase, PKCe ( epsilon isoform of protein kinase-C )
Jeon et al., Biochim Biophys Acta 2013 (Breast Neoplasms...) : When SelW was down-regulated, mTORC2 dependent phosphorylation of Akt at Ser473 was decreased
Melnik et al., Exp Dermatol 2013 : Antiandrogens may attenuate mTORC1 by suppressing mTORC2 mediated Akt/TSC2 signalling
Wang et al., PloS one 2013 : Western blotting showed that the PP242 inhibition of mTORC2 mediated AKT phosphorylation at Ser 473 ( AKT ( S473 ) ) was transient only in the first few hours of the PP242 treatment