Affinage

RICTOR

Rapamycin-insensitive companion of mTOR · UniProt Q6R327

Length
1708 aa
Mass
192.2 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RICTOR is the defining scaffold subunit of mTOR complex 2 (mTORC2), where it positions mTOR to phosphorylate the hydrophobic motif of AGC kinases—most notably Akt at Ser473, which in turn licenses Thr308 phosphorylation by PDK1 (PMID:15718470, PMID:16221682), as well as PKCα Ser657 and SGK1 (PMID:18089801, PMID:28453552). mTORC2 substrate selection is intrinsic to the complex architecture: cryo-EM structures show Rictor–mTOR side-chain contacts that sterically occlude mTORC1 substrates and confer rapamycin resistance, while mSin1 makes extensive contacts with Rictor and undergoes a conformational switch (rotation of Arg83) that selectively gates SGK1 versus Akt phosphorylation (PMID:35926713). Sin1 is itself an obligate mTORC2 subunit required for Rictor–mTOR integrity and for the selective downstream phosphorylation of FoxO transcription factors (PMID:16962653). Genetic dissection across organisms places Rictor/TORC2 upstream of both Akt and SGK, with SGK1 the primary effector for growth and metabolic phenotypes in C. elegans and the Akt–FoxO axis the principal pro-survival output in mammalian tissues such as the ovary (PMID:19240135, PMID:19260765, PMID:25564616). mTORC2 assembly and Rictor abundance are tightly regulated: USP9X removes Lys63-linked ubiquitin from Rictor to promote mTOR binding (PMID:33378666), GSK3 phosphorylates Rictor at Thr1695 within a phosphodegron to trigger FBXW7-mediated proteasomal degradation (PMID:25897075), glucose/acetate-driven acetylation creates a nutrient-sensitive autoactivation loop (PMID:26170313), and mTORC1–S6K1 imposes negative feedback by phosphorylating Rictor at Thr1135 to recruit 14-3-3 (PMID:19995915, PMID:19935711). Independently of mTORC2, Rictor assembles distinct complexes—with Myo1c, ILK, PKCζ, and Cullin-1/FBXW7—to control cortical actin remodeling, chemotaxis, and the ubiquitin-dependent turnover of SGK1, c-Myc, and cyclin E (PMID:18426911, PMID:18339839, PMID:20978191, PMID:21204013, PMID:22285861).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2005 High

    Established that the Rictor–mTOR complex is the long-sought Ser473 kinase for Akt, defining mTORC2 as a direct effector kinase rather than merely a scaffold.

    Evidence In vitro kinase reconstitution and RNAi of rictor/mTOR in human and Drosophila cells, plus an immunoprecipitation kinase assay in insulin-responsive adipocytes

    PMID:15718470 PMID:16221682

    Open questions at the time
    • Did not resolve how PIP3/insulin signals are transduced to activate the complex
    • Structural basis of substrate recognition unknown at this stage
  2. 2005 High

    Defined the substrate determinants that distinguish mTORC2 from mTORC1, showing rictor-mTOR selects rapamycin-resistant substrates independent of the TOR signaling motif.

    Evidence In vitro kinase assays with purified raptor-mTOR and rictor-mTOR complexes and S6K1 domain-deletion mutants

    PMID:15809305

    Open questions at the time
    • Did not identify the structural feature on Rictor responsible for discrimination
    • In-cell physiological relevance of S6K1 as an mTORC2 substrate not established
  3. 2006 High

    Identified Sin1 as an obligate mTORC2 subunit required for complex integrity and Akt Ser473 phosphorylation, and demonstrated selectivity of mTORC2's downstream signaling toward FoxO.

    Evidence sin1 genetic knockout, reciprocal co-IP for complex integrity, and phospho-specific immunoblotting of multiple Akt substrates

    PMID:16962653

    Open questions at the time
    • How Sin1 stabilizes the Rictor–mTOR interface not structurally defined
    • Did not explain why only a subset of Akt substrates depend on Ser473
  4. 2007 High

    In vivo genetic loss-of-function separated TORC2/rictor (Akt-FOXO) from TORC1/raptor (S6K) functions, fixing the pathway architecture in a whole organism.

    Evidence Drosophila rictor-null mutants with phospho-immunoblotting and cell size/apoptosis readouts

    PMID:17462592

    Open questions at the time
    • Tissue-specific contributions not dissected
    • Did not address mTORC2-independent rictor functions
  5. 2009 High

    Resolved the pathway hierarchy in C. elegans, showing rictor/TORC2 acts upstream of AKT and SGK with SGK-1 as the primary effector for growth and fat metabolism—revealing effector usage is tissue- and species-dependent.

    Evidence Forward genetics, epistasis with akt-1/akt-2/sgk-1 double mutants, gain-of-function sgk-1 suppressors, and tissue-specific rescue

    PMID:19240135 PMID:19260765

    Open questions at the time
    • Whether SGK1 dominance generalizes to mammalian tissues left open
    • Molecular basis of effector choice not determined
  6. 2009 High

    Uncovered an mTORC1→mTORC2 feedback loop in which S6K1 directly phosphorylates Rictor at Thr1135 to recruit 14-3-3, integrating the two complexes.

    Evidence In vitro S6K1 kinase assays, phospho-site mapping, T1135A mutant analysis, and 14-3-3 binding assays in two independent labs

    PMID:19935711 PMID:19995915

    Open questions at the time
    • The two reports differed on whether Thr1135 alters mTORC2 kinase activity
    • Physiological consequences of 14-3-3 sequestration incompletely defined
  7. 2008 Medium

    Demonstrated mTORC2-independent functions of Rictor in cytoskeletal regulation by identifying distinct complexes with Myo1c and ILK that control actin remodeling and paxillin/ILK-associated phosphorylation.

    Evidence Co-IP showing complexes distinct from mTOR, yeast two-hybrid mapping of direct ILK binding, colocalization, and rapamycin/wortmannin-insensitive functional assays

    PMID:18339839 PMID:18426911

    Open questions at the time
    • Single-lab findings for each complex
    • Kinase responsible for paxillin Tyr118 in the Myo1c complex not identified
  8. 2010 Medium

    Revealed Rictor moonlighting as an E3 ligase component, forming Cullin-1– and FBXW7-based complexes that ubiquitinate SGK1, c-Myc, and cyclin E independently of mTORC2.

    Evidence Co-IP of Cullin/FBXW7, ubiquitination assays, rictor-/- MEFs, phosphomimetic mutants, and FBXW7 knockout rescue

    PMID:21204013 PMID:22285861

    Open questions at the time
    • Single-lab demonstrations of ligase activity
    • Whether Rictor confers substrate specificity or acts as an adaptor unclear
  9. 2015 High

    Defined a layered regulation of Rictor stability and activity through GSK3/FBXW7-mediated degradation, nutrient-driven acetylation, and SIRT1/thyroid-hormone deacetylation.

    Evidence In vitro GSK3 kinase assay with degron mutagenesis, acetyl-CoA manipulation in tumor models, and SIRT1-mTORC2 co-IP with deacetylation assays

    PMID:25897075 PMID:26170313 PMID:26453307

    Open questions at the time
    • Cross-talk between phospho-degron and acetylation switches not integrated
    • Acetylation site(s) and the writer/eraser enzymes only partly defined
  10. 2015 High

    Mammalian conditional knockouts established a tissue-specific rictor/mTORC2/Akt-Foxo pro-survival axis (oogenesis, spermatogenesis) and distinguished mTORC2 from mTORC1 roles in CNS myelination.

    Evidence Cell-type-specific Cre/loxP rictor (and comparative raptor) knockouts with phospho-immunoblotting, histology, and electron microscopy

    PMID:24671993 PMID:25564616 PMID:26360620

    Open questions at the time
    • Effector divergence (Akt vs SGK) across these tissues not systematically compared
    • Contribution of mTORC2-independent rictor actin functions in these phenotypes only partially separated
  11. 2020 High

    Identified USP9X-mediated Lys63 deubiquitination of Rictor as a growth-factor-regulated switch controlling mTORC2 assembly, adding a ubiquitin-dependent layer to complex formation.

    Evidence Reciprocal co-IP, linkage-specific ubiquitin immunoblotting, USP9X knockdown in cells and mice, and mTORC2 kinase assays

    PMID:33378666

    Open questions at the time
    • E3 ligase that deposits the K63 chains not identified
    • How growth factors regulate USP9X activity unresolved
  12. 2022 High

    Cryo-EM structures provided the structural basis for mTORC2 substrate selectivity and rapamycin resistance, showing how Rictor occludes mTORC1 substrates and how Sin1 conformational changes gate SGK1 versus Akt.

    Evidence Cryo-EM of apo and substrate-bound human mTORC2 with mSin1 R83A mutagenesis validating substrate-specific predictions

    PMID:35926713

    Open questions at the time
    • Structures of regulated states (phosphorylated/acetylated Rictor) not resolved
    • Dynamics of substrate loading and product release not captured
  13. 2024 Medium

    Extended Rictor/mTORC2 function to organelle quality control, showing it facilitates MARCH5-mediated K48 ubiquitination and degradation of BNIP3 to restrain mitophagy.

    Evidence Rictor knockout in endothelial cells and a transplant model, K48-linkage-specific BNIP3 ubiquitination assays, and MARCH5 interaction studies

    PMID:38769658

    Open questions at the time
    • Single-lab finding
    • Whether this requires mTORC2 kinase activity or a separate Rictor complex not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct regulatory inputs on Rictor (K63 deubiquitination, GSK3 phosphodegron, acetylation, S6K1 feedback) are integrated to set mTORC2 output in a given cell, and what determines Akt- versus SGK1-effector dominance across mammalian tissues, remains unresolved.
  • No integrated quantitative model of competing Rictor modifications
  • Mammalian rules governing AGC-kinase effector choice undefined
  • Relationship between mTORC2-dependent and mTORC2-independent Rictor complexes in vivo unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0016874 ligase activity 2
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2 R-HSA-5357801 Programmed Cell Death 2
Partners
CUL1FBXW7ILKMAPKAP1 (SIN1)MTORMYO1CPRKCZUSP9X
Complex memberships
Rictor-Cullin-1 E3 ligaseRictor-FBXW7 E3 ligaseRictor-Myo1c complexmTORC2

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 The rictor-mTOR complex directly phosphorylates Akt/PKB on Ser473 in vitro, and rictor and mTOR are necessary for Ser473 phosphorylation in Drosophila and human cells; the rictor-mTOR complex also facilitates Thr308 phosphorylation by PDK1. In vitro kinase assay (rictor-mTOR complex phosphorylating Akt Ser473), RNAi knockdown of rictor/mTOR in human and Drosophila cells measuring Akt phosphorylation Science High 15718470
2005 The rictor-mTOR complex (mTORC2) phosphorylates the hydrophobic motif (Thr389) of rapamycin-resistant S6K1 mutants in vitro, whereas the raptor-mTOR complex (mTORC1) phosphorylates rapamycin-sensitive forms; substrate selection by rictor-mTOR is independent of the TOR signaling motif and depends on removal of the C-terminal domain of S6K1. In vitro kinase assays with purified raptor-mTOR and rictor-mTOR complexes and S6K1 mutants The Journal of biological chemistry High 15809305
2005 In 3T3-L1 adipocytes, mTOR complexed to RICTOR is the Ser473 kinase for Akt; vesicles immunoprecipitated with anti-mTOR or anti-RICTOR antibodies showed PIP3-stimulated Ser473 activity sensitive to wortmannin but not staurosporine, and RICTOR siRNA knockdown suppressed insulin-activated Ser473 phosphorylation. Subcellular fractionation, immunoprecipitation kinase assay, siRNA knockdown in 3T3-L1 adipocytes The Journal of biological chemistry High 16221682
2006 SIN1/MIP1 is an essential mTORC2 subunit; genetic ablation of sin1 abolished Akt Ser473 phosphorylation and disrupted rictor-mTOR interaction while leaving Thr308 phosphorylation intact. Loss of Ser473 phosphorylation selectively impaired FoxO1/3a phosphorylation but not TSC2, GSK3, S6K, or 4E-BP1, demonstrating substrate selectivity of mTORC2 downstream signaling. sin1 genetic knockout, co-immunoprecipitation to assess rictor-mTOR complex integrity, phospho-specific immunoblotting for Akt and Akt substrates Cell High 16962653
2006 During human cytomegalovirus (HCMV) infection, the rictor-containing mTOR complex is activated (elevated Akt Ser473 phosphorylation in a rapamycin-insensitive, caffeine-sensitive manner), and rictor is more significant than raptor for viral infection; depletion shows that in HCMV-infected cells both raptor and rictor complexes acquire altered substrate specificities and rapamycin sensitivities. shRNA depletion of rictor and raptor, phospho-immunoblotting, viral growth assays Proceedings of the National Academy of Sciences of the United States of America Medium 16959881
2007 In Drosophila rictor-null mutants, Akt-Ser505 phosphorylation is decreased, FOXO-dependent apoptosis is augmented, and Akt-induced tissue hyperplasia is reduced, while S6K phosphorylation and S6K-induced cell overgrowth are unaffected, demonstrating that rictor/TORC2 specifically regulates the Akt-FOXO signaling module distinct from raptor/TORC1-S6K signaling. Drosophila rictor-null genetic mutants, phospho-specific immunoblotting, cell size/apoptosis measurements Biochemical and biophysical research communications High 17462592
2007 Overexpression of rictor in glioma cell lines leads to increased mTORC2 assembly and activity, increased PKCα activity, and increased anchorage-independent growth, S-phase distribution, motility, and integrin β1/β3 expression; siRNA knockdown of rictor inhibited these phenotypes and reduced PKCα activity. Rictor overexpression and siRNA knockdown, mTORC2 kinase assays, soft agar growth, cell cycle analysis, PKCα activity assay, xenograft studies Cancer research Medium 18089801
2007 Rictor negatively regulates mTORC1 activity: shRNA-mediated downregulation of rictor increased S6K1 and 4E-BP1 phosphorylation and basal protein synthesis in TGFβ-treated renal cells, while raptor shRNA inhibited these effects, placing mTORC2/rictor as a negative regulator of mTORC1 to control basal protein synthesis. shRNA knockdown of raptor or rictor, phospho-immunoblotting of S6K and 4E-BP1, [35S]-methionine protein synthesis assay Cellular signalling Medium 18068336
2008 Rictor interacts directly with integrin-linked kinase (ILK); yeast two-hybrid assays showed a direct interaction between the NH2- and COOH-terminal domains of rictor and the ILK kinase domain. ILK and rictor colocalize in membrane ruffles and leading edges of cancer cells, and rictor regulates ILK-associated Akt Ser473 phosphorylation. Proteomic screen, co-immunoprecipitation, yeast two-hybrid, colocalization imaging, siRNA knockdown Cancer research Medium 18339839
2008 Rictor forms a complex with Myo1c (a molecular motor) in adipocytes that is biochemically distinct from mTORC2 and can be immunoprecipitated independently of mTOR. Loss of either rictor or Myo1c inhibits paxillin Tyr118 phosphorylation and Myo1c-induced membrane ruffling, effects that are rapamycin- and wortmannin-insensitive, indicating a mTORC2-independent role of rictor in cortical actin remodeling. Co-immunoprecipitation, RNAi knockdown, phospho-paxillin immunoblotting, membrane ruffling assay, rapamycin/wortmannin treatment Molecular and cellular biology Medium 18426911
2008 Hsp70 physically associates with rictor and is required for mTORC2 formation and activity; in cells with antisense RNA targeting Hsp70, mTORC2 assembly and mTORC2 kinase activity were impaired, while mTORC1 was unaffected. Yeast two-hybrid screen, co-immunoprecipitation, colocalization, mTORC2 kinase assay in Hsp70-depleted cells Biochemical and biophysical research communications Medium 18505677
2009 S6K1 (p70 ribosomal S6 kinase 1) directly phosphorylates rictor on Thr1135 in vitro and in vivo in a rapamycin-sensitive manner; cells expressing rictor T1135A have increased mTORC2-dependent Akt phosphorylation and increased phosphorylation of FoxO1/3a and GSK3, demonstrating that S6K1-mediated phosphorylation of rictor on Thr1135 inhibits mTORC2 activity as a feedback mechanism from mTORC1. In vitro S6K1 kinase assay with rictor, phospho-site mapping, rapamycin treatment in cells, T1135A phospho-dead mutant expression, phospho-immunoblotting Molecular and cellular biology High 19995915
2009 S6K1 directly phosphorylates rictor on Thr1135 (a conserved vertebrate site) via a rapamycin-sensitive cascade; Thr1135 phosphorylation mediates 14-3-3 binding to rictor/mTORC2 but does not cause major changes in mTORC2 kinase activity. In vitro S6K1 kinase assay, phosphorylation site mapping, 14-3-3 binding assay, mTORC2 kinase assay Oncogene High 19935711
2009 In C. elegans, rictor/TORC2 controls fat storage, body size, growth, feeding, reproduction, and lifespan; these phenotypes are genetically dependent on akt-1, akt-2, and sgk-1, with fat metabolism and growth principally mediated by sgk-1 in the intestine, placing rictor upstream of AKT and SGK in a tissue-specific manner. Forward genetic screen, rictor loss-of-function mutants, epistasis analysis with akt-1, akt-2, sgk-1 double mutants, tissue-specific rescue experiments Genes & development High 19240135
2009 In C. elegans, loss of CeRictor phenocopies loss of sgk-1 (not akt), and a gain-of-function sgk-1 mutation suppresses CeRictor mutant phenotypes (developmental delay, decreased body size, increased lipid storage), establishing SGK1 as the primary mediator of TORC2 in regulating growth and metabolism, distinct from AKT. Loss-of-function mutant analysis, epistasis with sgk-1 and akt double mutants, gain-of-function sgk-1 suppressor analysis PLoS biology High 19260765
2010 FoxO1 transcription factor induces rictor gene expression, increasing mTORC2 assembly and activity, which subsequently activates Akt; in Tsc2-deficient cells, FoxO1-induced rictor elevation increases mTORC2 at the expense of mTORC1, creating a feedback loop. Overexpression/knockdown of FoxO1, rictor expression measurements, mTORC2 kinase assays, genetic epistasis with Tsc2-/- cells Developmental cell Medium 20412774
2010 Rictor interacts with PKCζ, and EGF induces translocation and colocalization of rictor with PKCζ independently of the mTORC2 complex; rictor knockdown inhibited EGF-induced PKCζ phosphorylation and translocation, phosphorylation of cofilin, and cellular chemotaxis, and ablated pulmonary metastasis in a xenograft model. Co-immunoprecipitation, colocalization imaging, siRNA knockdown, chemotaxis assay, xenograft metastasis model Cancer research Medium 20978191
2010 Rictor suppresses RhoGDI2 protein levels by a mechanism independent of Sin1 and raptor (hence independent of mTORC2 and mTORC1), and this rictor-dependent suppression of RhoGDI2 promotes Rac and Cdc42 activity and cell migration. Proteomics, rictor/sin1/raptor knockdown, Rac/Cdc42 activity assays, RhoGDI2 expression analysis, migration assays Oncogene Medium 22777355
2010 Rictor contains a novel ubiquitin E3 ligase activity by forming a complex with Cullin-1 (but not other Cullins); SGK1 is identified as a substrate of this Rictor/Cullin-1 E3 ligase. Phosphorylation of rictor at Thr1135 by AGC kinases (Akt, S6K, SGK1) disrupts Rictor-Cullin-1 interaction, impairing SGK1 ubiquitination and leading to SGK1 accumulation. Co-immunoprecipitation of Cullin proteins, ubiquitination assays, rictor-/- MEFs, T1135E phosphomimetic mutant, SGK1 stability assays Protein & cell Medium 21204013
2012 Rictor associates with FBXW7 to form an E3 ligase complex (distinct from mTORC2) that mediates ubiquitination and degradation of c-Myc and cyclin E; rictor knockdown decreased ubiquitination and increased c-Myc and cyclin E levels, while FBXW7 knockout blocked rictor's effects on these substrates. Co-immunoprecipitation, rictor overexpression/knockdown, FBXW7 knockout, ubiquitination assays, c-Myc and cyclin E protein stability Biochemical and biophysical research communications Medium 22285861
2013 IKKα and IKKβ physically interact with rictor (in vitro binding mapped to rictor amino acids 999–1397); chemical or genetic inhibition of IKK reduced Akt Ser473 and PKCα Ser657 phosphorylation and decreased mTORC2 kinase activity; inactive IKK competed with mTOR for rictor binding, reducing mTORC2 levels and activity. Co-immunoprecipitation, in vitro binding assay with rictor fragments, siRNA knockdown, kinase-dead IKK expression, mTORC2 kinase assay Cellular signalling Medium 23872070
2013 Rictor/Sin1 complexes are required for type I interferon-induced STAT pathway activation; knockdown of rictor or Sin1 resulted in defective STAT activation, reduced STAT-DNA binding, and decreased IFN-inducible gene expression, establishing a role for mTORC2 in IFN signaling. Stable and transient rictor/Sin1 knockdown, STAT phosphorylation assays, STAT-DNA binding (EMSA), IFN-inducible gene expression The Journal of biological chemistry Medium 24469448
2014 Conditional deletion of rictor in CNS oligodendrocytes revealed that mTORC2/rictor ablation has a modest positive effect on oligodendrocyte differentiation and very little effect on myelination when mTORC1 is intact, whereas raptor (mTORC1) ablation causes significant dysmyelination; this establishes distinct roles of the two mTOR complexes in CNS myelination. Conditional Cre/loxP knockout of rictor or raptor in oligodendrocyte lineage, histology, electron microscopy, myelin protein immunoblotting The Journal of neuroscience Medium 24671993
2015 GSK3 phosphorylates rictor at Thr1695 (within a CDC4 phospho-degron motif), promoting interaction between rictor and the E3 ubiquitin ligase FBXW7 and subsequent rictor ubiquitination and proteasomal degradation; mutation of Thr1695 impaired FBXW7 binding and stabilized rictor. Akt activation enhanced rictor levels by suppressing GSK3-dependent rictor degradation. In vitro GSK3 kinase assay on rictor, co-IP of FBXW7 and rictor, proteasome inhibitor treatment, T1695A/E mutagenesis, FBXW7 overexpression/knockout The Journal of biological chemistry High 25897075
2015 Glucose or acetate promotes acetyl-CoA-dependent acetylation of rictor, which activates mTORC2 and creates an autoactivation loop maintaining mTORC2 activity even when upstream growth factor receptor components are inactive, rendering GBM cells resistant to EGFR/PI3K/AKT-targeted therapies. Cell line and mouse tumor models, acetylation assays of rictor, acetyl-CoA manipulation, pharmacological inhibition of upstream signaling Proceedings of the National Academy of Sciences of the United States of America Medium 26170313
2015 Thyroid hormone (TH) increases SIRT1-mTORC2 interaction and promotes RICTOR deacetylation, leading to decreased AKT and FOXO1 phosphorylation; this increases FOXO1 nuclear localization and target gene transcription, demonstrating that RICTOR deacetylation is a mechanism linking TH signaling to mTORC2-AKT-FOXO1 axis. SIRT1-mTORC2 co-IP, RICTOR deacetylation assays, AKT and FOXO1 phospho-immunoblotting, hepatic transcriptome profiling The Journal of biological chemistry Medium 26453307
2015 Rictor/mTORC2 signaling in oocytes is required for folliculogenesis and follicle survival; oocyte-specific rictor knockout mice exhibited premature ovarian failure, massive follicular death, reduced Akt Ser473 phosphorylation, reduced Foxo3a phosphorylation, and elevated pro-apoptotic proteins, establishing a rictor/mTORC2/Akt/Foxo3a pro-survival axis in folliculogenesis. Conditional oocyte-specific rictor knockout (Cre/loxP), phospho-immunoblotting, apoptosis markers, ovarian histology The Journal of biological chemistry High 25564616
2015 Conditional deletion of rictor in Sertoli cells causes azoospermia and sterility; rictor regulates actin organization via both mTORC2-dependent (Rac1 GTPase) and mTORC2-independent (paxillin phosphorylation) mechanisms, and loss of rictor disrupts Sertoli cell polarity, BTB integrity, and spermatogenesis. Conditional Sertoli cell-specific rictor knockout, actin filament staining, Rac1 activity assay, paxillin phospho-immunoblotting, electron microscopy Endocrinology Medium 26360620
2015 Rictor regulates actin cytoskeleton organization via RhoA-GTPase; resveratrol-mediated downregulation of rictor in A431 cells reduced RhoA-GTPase activity and altered actin cytoskeleton, and exogenous overexpression of rictor restored RhoA activity and actin network, establishing a direct role of rictor in RhoA-mediated actin organization. Rictor overexpression/knockdown, RhoA-GTPase activity assay, actin cytoskeleton staining, senescence assay Photochemistry and photobiology Low 22272775
2015 SMAD4 physically interacts with and inhibits RICTOR; SMAD4 deficiency activates mTORC2/AKT Ser473 signaling, and overexpression of SMAD4 or depletion of RICTOR suppresses AKT signaling and increases irinotecan sensitivity in SMAD4-deficient colon cancer cells. Co-immunoprecipitation of SMAD4 and RICTOR, SMAD4 overexpression and RICTOR depletion, phospho-AKT immunoblotting, cell viability and in vivo tumor assays Molecular cancer research Medium 31932471
2015 Tetraspanin 8 (Tspan8) forms a complex with rictor and integrin α3 in glioma cells; Tspan8-rictor association is required for mTORC2 activation; knockdown of Tspan8 prevented mTOR-rictor assembly and phosphorylation of AKT Ser473 and PKCα, and inhibited glioma cell migration. Co-immunoprecipitation, siRNA knockdown of Tspan8/rictor/integrin α3, mTORC2 assembly assay, AKT/PKCα phospho-immunoblotting, migration assay International journal of molecular sciences Medium 25761241
2015 In Saccharomyces cerevisiae, TSC11/AVO3 (rictor ortholog) is genetically linked to cell integrity regulation; temperature-sensitive tsc11 mutants show cell wall defects, and dosage suppression identifies functional interactions with AVO1, AVO2, PKC1, and SLM1 as TORC2 components, with Tsc11p acting via a Pkc1p-independent mechanism through Avo1p and a Pkc1p-dependent mechanism through Avo2p/Slm1p. Temperature-sensitive allele analysis, osmotic stabilizer rescue, dosage suppression genetics, cell wall integrity assays Current genetics Medium 15809876
2017 A small molecule (CID613034) that specifically blocks the rictor-mTOR protein-protein interaction inhibited mTORC2 kinase activity at submicromolar concentrations in vitro, selectively blocked phosphorylation of mTORC2 substrates (AKT Ser473, NDRG1 Thr346, PKCα Ser657) without affecting mTORC1 substrate S6K phosphorylation, and had anti-tumor effects in GBM xenografts. High-throughput yeast two-hybrid screen, in vitro mTORC2 kinase assay, phospho-selective immunoblotting in cells, xenograft tumor model PloS one Medium 28453552
2017 mTORC2/AKT signaling activates HSF1, which induces HuR expression; HuR directly binds the 3'UTR of the rictor transcript to enhance its translational efficiency, creating a feed-forward loop in which mTORC2 activity drives rictor expression in GBM. HuR-rictor 3'UTR binding assay, RNAi of AKT/HSF1/HuR, rictor protein/mRNA measurements, xenograft tumor growth Oncogene Medium 29059166
2018 In vascular smooth muscle cells, TGFβ activates rictor in an integrin-linked kinase (ILK)-dependent manner, and β3-integrin expression modulates TGFβ-induced rictor phosphorylation (Thr1135); rictor activation is associated with an altered proliferative-migratory and metabolic phenotype resembling the aneurysm phenotype in Marfan syndrome aorta. Proteomics of MFS mouse aorta (data-independent acquisition MS), Western blot validation of rictor Thr1135 phosphorylation in vivo, ILK inhibition and β3-integrin manipulation in cultured aortic vascular smooth muscle cells American journal of physiology. Heart and circulatory physiology Medium 30004239
2020 USP9X deubiquitinase removes Lys63-linked ubiquitin from RICTOR to promote its interaction with mTOR, thereby facilitating mTORC2 assembly and activity; growth factors regulate USP9X activity to stimulate mTORC2 assembly, establishing a ubiquitin-dependent mechanism for mTORC2 complex formation. Co-IP of USP9X and RICTOR, ubiquitin linkage-specific immunoblotting, USP9X knockdown in human cell lines and mice, mTORC2 kinase activity assay Cell reports High 33378666
2020 Rictor interacts with ABLIM1 and regulates its serine phosphorylation (at Ser214 and Ser431); dominant-negative mutations at these sites inhibited ABLIM1-mediated actin polymerization and MKL1/SRF-dependent transcription (Arp3, c-Fos), linking rictor to actin dynamics through ABLIM1 phosphorylation in HCC cells. Co-immunoprecipitation, ABLIM1 knockout cell lines, phospho-site mutation (S214A, S431A), actin polymerization assay, MKL1 nuclear translocation imaging, SRF reporter assay International journal of biological sciences Medium 33061800
2022 Cryo-EM structures of human mTORC2 in apo form and in complex with substrates Akt and SGK1 revealed: (1) Rictor-mTOR side chain interactions that sterically occlude mTORC1 substrates and confer rapamycin resistance; (2) mSin1 forms extensive contacts with Rictor via α-helices and an extended strand; (3) SGK1 (but not Akt) markedly alters mSin1 N-terminal conformation, inducing rotation of mSin1 Arg83 to interact with negatively charged Rictor residues; mutation of mSin1 Arg83 to Ala selectively disrupts mTORC2 phosphorylation of SGK1 but not Akt. Cryo-EM structure determination of human mTORC2 apo and substrate-bound complexes, functional phosphorylation assays with mSin1 R83A mutant The Journal of biological chemistry High 35926713
2022 mTORC2 inactivation (via rictor deletion) in the inner ear is the major driver of sensorineural hearing loss induced by high-dose sirolimus; mTORC2 exerts its effects primarily through AKT phosphorylation, and ablation of P53 activity greatly attenuated hearing loss severity in mTORC2-deficient mice; selective activation of mTORC2 protects against acoustic trauma and cisplatin-induced ototoxicity. Pharmacological and genetic interventions in murine hearing models, rictor conditional knockout, p53 knockout epistasis, auditory brainstem response testing, AKT phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America Medium 35238644
2024 Rictor/mTORC2 facilitates MARCH5-mediated K48-linked ubiquitination and degradation of BNIP3 at the K130 site, thereby reducing BNIP3-dependent mitophagy; rictor knockout increases BNIP3-mediated mitophagy in endothelial cells, ameliorates EndMT, and reduces allograft interstitial fibrosis. Rictor knockout in endothelial cells and in allogeneic kidney transplant mouse model, BNIP3 ubiquitination assays (K48 linkage-specific), MARCH5 interaction studies, mitophagy assays, histology of renal fibrosis Clinical and translational medicine Medium 38769658

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science (New York, N.Y.) 5546 15718470
2006 SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 1161 16962653
2005 mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes. The Journal of biological chemistry 528 16221682
2009 mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling. Molecular and cellular biology 353 19995915
2009 Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans. Genes & development 338 19240135
2010 FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor. Developmental cell 300 20412774
2007 mTORC2 activity is elevated in gliomas and promotes growth and cell motility via overexpression of rictor. Cancer research 209 18089801
2008 Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival. Cancer research 197 18339839
2009 Rictor/TORC2 regulates Caenorhabditis elegans fat storage, body size, and development through sgk-1. PLoS biology 158 19260765
2014 Conditional ablation of raptor or rictor has differential impact on oligodendrocyte differentiation and CNS myelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 144 24671993
2011 Rictor/mTORC2 is essential for maintaining a balance between beta-cell proliferation and cell size. Diabetes 129 21266327
2009 Rictor is a novel target of p70 S6 kinase-1. Oncogene 127 19935711
2005 Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif site. The Journal of biological chemistry 118 15809305
2010 mTOR complex component Rictor interacts with PKCzeta and regulates cancer cell metastasis. Cancer research 115 20978191
2015 Glucose-dependent acetylation of Rictor promotes targeted cancer therapy resistance. Proceedings of the National Academy of Sciences of the United States of America 103 26170313
2021 An RNA-RNA crosstalk network involving HMGB1 and RICTOR facilitates hepatocellular carcinoma tumorigenesis by promoting glutamine metabolism and impedes immunotherapy by PD-L1+ exosomes activity. Signal transduction and targeted therapy 94 34916485
2006 Human cytomegalovirus infection alters the substrate specificities and rapamycin sensitivities of raptor- and rictor-containing complexes. Proceedings of the National Academy of Sciences of the United States of America 91 16959881
2020 TELO2 induced progression of colorectal cancer by binding with RICTOR through mTORC2. Oncology reports 83 33416177
2016 Integrin-α10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma. Cancer discovery 78 27577794
2015 Rictor/mTORC2 signaling mediates TGFβ1-induced fibroblast activation and kidney fibrosis. Kidney international 77 25970154
2014 Rictor/mTORC2 protects against cisplatin-induced tubular cell death and acute kidney injury. Kidney international 75 24451322
2016 Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers. Cancer research 74 27197158
2013 MiR-424/503-mediated Rictor upregulation promotes tumor progression. PloS one 69 24244675
2017 Specific blockade of Rictor-mTOR association inhibits mTORC2 activity and is cytotoxic in glioblastoma. PloS one 68 28453552
2013 Requirement for Rictor in homeostasis and function of mature B lymphoid cells. Blood 65 23958952
2015 Rictor/mTORC2 pathway in oocytes regulates folliculogenesis, and its inactivation causes premature ovarian failure. The Journal of biological chemistry 64 25564616
2015 Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7-mediated Ubiquitination and Proteasomal Degradation. The Journal of biological chemistry 63 25897075
2008 Hsp70 associates with Rictor and is required for mTORC2 formation and activity. Biochemical and biophysical research communications 61 18505677
2007 Raptor-rictor axis in TGFbeta-induced protein synthesis. Cellular signalling 60 18068336
2015 PIA: An Intuitive Protein Inference Engine with a Web-Based User Interface. Journal of proteome research 58 25938255
2012 Rictor regulates cell migration by suppressing RhoGDI2. Oncogene 58 22777355
2017 RICTOR amplification identifies a subgroup in small cell lung cancer and predicts response to drugs targeting mTOR. Oncotarget 55 27863413
2008 A Rictor-Myo1c complex participates in dynamic cortical actin events in 3T3-L1 adipocytes. Molecular and cellular biology 55 18426911
2018 Unmasking the impact of Rictor in cancer: novel insights of mTORC2 complex. Carcinogenesis 52 29955840
2023 VE-cadherin in arachnoid and pia mater cells serves as a suitable landmark for in vivo imaging of CNS immune surveillance and inflammation. Nature communications 51 37730744
2018 The role of RICTOR downstream of receptor tyrosine kinase in cancers. Molecular cancer 51 29455662
2010 Rictor regulates MMP-9 activity and invasion through Raf-1-MEK-ERK signaling pathway in glioma cells. Molecular carcinogenesis 51 21557327
2007 Rapamycin regulates the phosphorylation of rictor. Biochemical and biophysical research communications 50 17707343
2015 Autophagy-related genes Raptor, Rictor, and Beclin1 expression and relationship with multidrug resistance in colorectal carcinoma. Human pathology 49 26363527
2016 Loss of Rictor with aging in osteoblasts promotes age-related bone loss. Cell death & disease 47 27735936
2012 Resveratrol-mediated downregulation of Rictor attenuates autophagic process and suppresses UV-induced skin carcinogenesis. Photochemistry and photobiology 47 22272775
2015 Rictor Regulates Spermatogenesis by Controlling Sertoli Cell Cytoskeletal Organization and Cell Polarity in the Mouse Testis. Endocrinology 46 26360620
2012 Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells. Biochemical and biophysical research communications 46 22285861
2015 The PTEN-AKT-mTOR/RICTOR Pathway in Nasal Natural Killer Cell Lymphoma Is Activated by miR-494-3p via PTEN But Inhibited by miR-142-3p via RICTOR. The American journal of pathology 45 25907832
2015 Hepatic FOXO1 Target Genes Are Co-regulated by Thyroid Hormone via RICTOR Protein Deacetylation and MTORC2-AKT Protein Inhibition. The Journal of biological chemistry 45 26453307
2018 Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity in C. elegans. PLoS genetics 44 29415022
2016 Targeted Inhibition of Rictor/mTORC2 in Cancer Treatment: A New Era after Rapamycin. Current cancer drug targets 44 26563881
2017 mTORC2/AKT/HSF1/HuR constitute a feed-forward loop regulating Rictor expression and tumor growth in glioblastoma. Oncogene 42 29059166
2017 Rictor regulates the vasculogenic mimicry of melanoma via the AKT-MMP-2/9 pathway. Journal of cellular and molecular medicine 41 28699701
2013 Murine dendritic cell rapamycin-resistant and rictor-independent mTOR controls IL-10, B7-H1, and regulatory T-cell induction. Blood 41 23444404
2018 MicroRNA-let-7a regulates cell autophagy by targeting Rictor in gastric cancer cell lines MGC-803 and SGC-7901. Oncology reports 38 29328491
2022 Activation of Rictor/mTORC2 signaling acts as a pivotal strategy to protect against sensorineural hearing loss. Proceedings of the National Academy of Sciences of the United States of America 35 35238644
2017 Inhibition of mTORC2 component RICTOR impairs tumor growth in pancreatic cancer models. Oncotarget 35 28445935
2023 RBM45 reprograms lipid metabolism promoting hepatocellular carcinoma via Rictor and ACSL1/ACSL4. Oncogene 34 38040804
2015 Tetraspanin 8-rictor-integrin α3 complex is required for glioma cell migration. International journal of molecular sciences 34 25761241
2015 mTORC2/rictor signaling disrupts dopamine-dependent behaviors via defects in striatal dopamine neurotransmission. The Journal of neuroscience : the official journal of the Society for Neuroscience 34 26063917
2013 IKK interacts with rictor and regulates mTORC2. Cellular signalling 34 23872070
2022 Interactions between mTORC2 core subunits Rictor and mSin1 dictate selective and context-dependent phosphorylation of substrate kinases SGK1 and Akt. The Journal of biological chemistry 32 35926713
2019 Upregulation of microRNA-424 relieved diabetic nephropathy by targeting Rictor through mTOR Complex2/Protein Kinase B signaling. Journal of cellular physiology 32 30637733
2018 Protein Inference Using PIA Workflows and PSI Standard File Formats. Journal of proteome research 32 30474983
2012 Inducible raptor and rictor knockout mouse embryonic fibroblasts. Methods in molecular biology (Clifton, N.J.) 32 22125071
2007 Discrete functions of rictor and raptor in cell growth regulation in Drosophila. Biochemical and biophysical research communications 32 17462592
2021 Cell-Penetrating Peptide-Modified Graphene Oxide Nanoparticles Loaded with Rictor siRNA for the Treatment of Triple-Negative Breast Cancer. Drug design, development and therapy 30 34916779
2016 microRNA-153 Targets mTORC2 Component Rictor to Inhibit Glioma Cells. PloS one 30 27295037
2005 Saccharomyces cerevisiaeTSC11/AVO3 participates in regulating cell integrity and functionally interacts with components of the Tor2 complex. Current genetics 30 15809876
2016 Rictor/mTORC2 loss in osteoblasts impairs bone mass and strength. Bone 29 27262777
2020 The role of RICTOR amplification in targeted therapy and drug resistance. Molecular medicine (Cambridge, Mass.) 28 32041519
2019 Disruption of the RICTOR/mTORC2 complex enhances the response of head and neck squamous cell carcinoma cells to PI3K inhibition. Molecular oncology 28 31393061
2017 Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin. PLoS biology 28 28821013
2015 RICTOR involvement in the PI3K/AKT pathway regulation in melanocytes and melanoma. Oncotarget 28 26356562
2014 Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes of Patients with Hepatocellular Carcinoma. Digestive diseases and sciences 28 25371154
1997 Ganglionic axons in motor roots and pia mater. Progress in neurobiology 27 9247961
2020 RICTOR/mTORC2 affects tumorigenesis and therapeutic efficacy of mTOR inhibitors in esophageal squamous cell carcinoma. Acta pharmaceutica Sinica. B 26 32642408
2020 mTORC2 Assembly Is Regulated by USP9X-Mediated Deubiquitination of RICTOR. Cell reports 26 33378666
2019 Micromechanical heterogeneity of the rat pia-arachnoid complex. Acta biomaterialia 26 31585202
2018 Inhibition of mTORC2/RICTOR Impairs Melanoma Hepatic Metastasis. Neoplasia (New York, N.Y.) 26 30404068
2018 Proteomics reveals Rictor as a noncanonical TGF-β signaling target during aneurysm progression in Marfan mice. American journal of physiology. Heart and circulatory physiology 25 30004239
2018 Opposing Tumor-Promoting and -Suppressive Functions of Rictor/mTORC2 Signaling in Adult Glioma and Pediatric SHH Medulloblastoma. Cell reports 24 29996106
2011 Alcohol-induced modulation of rictor and mTORC2 activity in C2C12 myoblasts. Alcoholism, clinical and experimental research 24 21438886
2017 Rictor/mTORC2 deficiency enhances keratinocyte stress tolerance via mitohormesis. Cell death and differentiation 23 28211872
2022 LncRNA KCNQ1OT1 promotes osteogenic differentiation via miR-205-5p/RICTOR axis. Experimental cell research 21 35341776
2018 Superhero Rictor promotes cellular differentiation of mouse embryonic stem cells. Cell death and differentiation 21 30154443
2017 Targeting mTORC2 component rictor inhibits cell proliferation and promotes apoptosis in gastric cancer. American journal of translational research 21 28979705
2015 Endothelial Rictor is crucial for midgestational development and sustained and extensive FGF2-induced neovascularization in the adult. Scientific reports 21 26635098
2021 mTOR-Rictor-EGFR axis in oncogenesis and diagnosis of glioblastoma multiforme. Molecular biology reports 20 34132942
2020 Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma. International journal of biological sciences 20 33061800
2018 Rictor deficiency in dendritic cells exacerbates acute kidney injury. Kidney international 20 30190173
2017 RICTOR expression in esophageal squamous cell carcinoma and its clinical significance. Medical oncology (Northwood, London, England) 19 28132115
2021 Vimentin loss promotes cancer proliferation through up-regulating Rictor/AKT/β-catenin signaling pathway. Experimental cell research 18 34052237
2019 MiR-152 influences osteoporosis through regulation of osteoblast differentiation by targeting RICTOR. Pharmaceutical biology 18 31492082
2014 Critical roles for Rictor/Sin1 complexes in interferon-dependent gene transcription and generation of antiproliferative responses. The Journal of biological chemistry 18 24469448
2024 Rictor/mTORC2 signalling contributes to renal vascular endothelial-to-mesenchymal transition and renal allograft interstitial fibrosis by regulating BNIP3-mediated mitophagy. Clinical and translational medicine 17 38769658
2023 The Ka /Ks and πa /πs Ratios under Different Models of Gametophytic and Sporophytic Selection. Genome biology and evolution 17 37561000
2020 Targeting RICTOR Sensitizes SMAD4-Negative Colon Cancer to Irinotecan. Molecular cancer research : MCR 17 31932471
2016 Purification and Evaluation of Polysaccharide Intercellular Adhesion (PIA) Antigen from Staphylococcus epidermidis. Current microbiology 17 27460584
2014 Transmembrane Inhibitor of RICTOR/mTORC2 in Hematopoietic Progenitors. Stem cell reports 17 25418727
2011 mTOR-rictor is the Ser473 kinase for AKT1 in mouse one-cell stage embryos. Molecular and cellular biochemistry 17 22057724
2020 Rictor-targeting exosomal microRNA-16 ameliorates lung fibrosis by inhibiting the mTORC2-SPARC axis. Experimental cell research 16 33307020
2019 Synthesis of conjugated PIA-rSesC and immunological evaluation against biofilm-forming Staphylococcus epidermidis. Journal of medical microbiology 16 30990402
2010 Phosphorylation of Rictor at Thr1135 impairs the Rictor/Cullin-1 complex to ubiquitinate SGK1. Protein & cell 16 21204013

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