Affinage

RICTOR

Rapamycin-insensitive companion of mTOR · UniProt Q6R327

Length
1708 aa
Mass
192.2 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RICTOR is the defining scaffolding subunit of mTOR complex 2 (mTORC2), where it assembles with mTOR, mLST8, SIN1, and Protor-1/2 to form a rapamycin-insensitive kinase complex that directly phosphorylates AGC-family kinases—Akt/PKB at Ser473, PKCα, and SGK1—at their hydrophobic motifs, thereby controlling cell survival, actin cytoskeleton organization, and metabolism (PMID:15268862, PMID:15718470, PMID:17141160, PMID:19240135). The RICTOR–SIN1 interaction, which requires Gly-934, is essential for mTORC2 assembly and Akt Ser473 phosphorylation, and loss of this interaction selectively impairs FOXO-dependent signaling without affecting mTORC1 outputs (PMID:16962653, PMID:21909137). RICTOR stability and mTORC2 activity are regulated by multiple post-translational mechanisms: S6K1 phosphorylates Thr1135 to create a 14-3-3 binding site that attenuates mTORC2-Akt signaling, GSK3 phosphorylates Thr1695 to trigger FBXW7-mediated proteasomal degradation, USP9X removes Lys63-linked ubiquitin chains to promote mTORC2 assembly, and glucose-dependent acetylation sustains mTORC2 activity independently of growth factor receptors (PMID:19995915, PMID:25897075, PMID:33378666, PMID:26170313). Beyond mTORC2, RICTOR forms an mTOR-independent E3 ligase complex with Cullin-1 that ubiquitinates SGK1 and associates with FBXW7 to promote degradation of c-Myc and cyclin E, and it regulates actin dynamics through Rac/Cdc42 GTPases and ezrin in an mTOR kinase-independent manner (PMID:21204013, PMID:24006489, PMID:28821013).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2004 High

    Identification of RICTOR as a novel mTOR-binding protein established the existence of a second, rapamycin-insensitive mTOR complex (mTORC2) distinct from raptor-containing mTORC1, resolving the long-standing question of how mTOR signals to the actin cytoskeleton via PKCα.

    Evidence Co-immunoprecipitation, mass spectrometry, siRNA knockdown, and actin cytoskeleton assays in mammalian cells

    PMID:15268862

    Open questions at the time
    • Kinase substrates of mTORC2 beyond PKCα not yet identified
    • No structural information on RICTOR or how it distinguishes mTORC2 from mTORC1
  2. 2005 High

    Demonstration that mTORC2 directly phosphorylates Akt at Ser473 resolved the decade-long search for 'PDK2' and established the central signaling output of the RICTOR-containing complex.

    Evidence In vitro kinase assay with purified rictor-mTOR complex, RNAi in Drosophila and human cells; complemented by in vitro phosphorylation of AGC kinase hydrophobic motifs on S6K1 mutants

    PMID:15718470 PMID:15809305

    Open questions at the time
    • Whether mTORC2 phosphorylates additional AGC kinases in vivo not yet determined
    • Mechanism of substrate recognition unknown
  3. 2006 High

    Genetic ablation of rictor and sin1 in mice demonstrated that SIN1 is essential for RICTOR-mTOR interaction and that mTORC2 selectively controls Akt-FOXO signaling without affecting mTORC1 substrates, establishing substrate selectivity in vivo.

    Evidence Mouse rictor-null and mLST8-null knockouts; sin1 genetic knockout with epistasis analysis of downstream phosphosubstrates

    PMID:16962653 PMID:17141160

    Open questions at the time
    • Structural basis of SIN1-RICTOR interaction unknown
    • How FOXO selectivity is achieved mechanistically unclear
  4. 2007 High

    Identification of Protor-1/2 as RICTOR-associated mTORC2 subunits and Drosophila rictor-null analysis confirmed the Akt-FOXO axis control and showed Protor is dispensable for core complex assembly, refining the subunit hierarchy.

    Evidence Reciprocal Co-IP with detergent fractionation for Protor; Drosophila rictor-null genetic analysis with phospho-Western and apoptosis assays

    PMID:17461779 PMID:17462592

    Open questions at the time
    • Function of Protor-1/2 within mTORC2 remains unknown
    • Whether Protor contributes to substrate specificity untested
  5. 2009 High

    Discovery that S6K1 phosphorylates RICTOR at Thr1135 in a rapamycin-sensitive manner, creating a 14-3-3 binding site that attenuates mTORC2-Akt signaling, established a negative feedback loop from mTORC1 to mTORC2.

    Evidence In vitro S6K1 kinase assay, phospho-specific antibody, T1135A mutant rescue, 14-3-3 pull-down, rapamycin treatment; independently confirmed by two groups

    PMID:19935711 PMID:19995915

    Open questions at the time
    • Precise mechanism by which 14-3-3 binding inhibits mTORC2 signaling not resolved
    • Whether additional kinases phosphorylate Thr1135 in specific contexts unclear
  6. 2009 High

    Genetic epistasis in C. elegans identified SGK-1 as the primary mTORC2/RICTOR effector for fat metabolism, growth, and lifespan, expanding the effector repertoire beyond Akt.

    Evidence Forward genetic screen, rictor loss-of-function mutants, epistasis with akt-1/akt-2/sgk-1, gain-of-function sgk-1 suppressor; two independent studies

    PMID:19240135 PMID:19260765

    Open questions at the time
    • Direct phosphorylation of SGK-1 by TORC2 not biochemically shown in worms
    • Whether SGK-1 mediates RICTOR functions in mammals to the same extent untested
  7. 2010 Medium

    Discovery that RICTOR forms an mTORC2-independent E3 ligase complex with Cullin-1 to ubiquitinate SGK1 revealed a non-kinase scaffolding function of RICTOR, with Thr1135 phosphorylation disrupting this complex as a feedback mechanism.

    Evidence Co-immunoprecipitation of Rictor-Cullin-1, in vitro ubiquitination assay, T1135E phosphomimetic, Rictor-null MEFs

    PMID:21204013

    Open questions at the time
    • Single-lab finding; independent replication needed
    • Whether Cullin-1-RICTOR targets substrates beyond SGK1 unknown
    • Structural basis of RICTOR as E3 ligase adaptor not determined
  8. 2011 High

    Identification of Gly-934 as critical for the RICTOR-SIN1 interface provided the first residue-level understanding of mTORC2 assembly, explaining a C. elegans fat-storage phenotype at the molecular level.

    Evidence Site-directed mutagenesis (G934E), Co-IP for complex components, Akt Ser473 phosphorylation and proliferation assays

    PMID:21909137

    Open questions at the time
    • No crystal structure of the RICTOR-SIN1 interface
    • Whether other residues near Gly-934 contribute to the interaction surface untested
  9. 2013 High

    Demonstration that RICTOR regulates actin polymerization and chemotaxis through Rac/Cdc42 independently of mTOR kinase activity and mSin1 uncoupled RICTOR's cytoskeletal functions from canonical mTORC2 kinase signaling.

    Evidence siRNA knockdown of Rictor vs. Raptor vs. mSin1, chemical mTOR inhibition, kinase-dead mutant, Rac/Cdc42 activity and actin assays in HL-60 cells

    PMID:24006489

    Open questions at the time
    • How RICTOR activates Rac/Cdc42 without mTOR kinase activity is mechanistically unclear
    • Whether this kinase-independent function occurs in non-hematopoietic cells untested
  10. 2013 High

    Conditional brain-specific RICTOR deletion linked mTORC2 to PKC isoform stability and neuronal morphology, demonstrating that RICTOR-dependent PKC phosphorylation controls cytoskeletal substrates GAP-43 and MARCKS in vivo.

    Evidence Purkinje cell-specific Cre/loxP knockout, phospho-Western for Akt/PKC/SGK1, immunohistochemistry, neuronal morphology analysis

    PMID:23569215

    Open questions at the time
    • Whether neuronal phenotypes are primarily PKC-mediated or also involve Akt/SGK1 not fully dissected
    • Rescue experiments with constitutively active PKC not performed
  11. 2015 High

    Identification of GSK3-mediated phosphorylation of RICTOR at Thr1695 as a phospho-degron recognized by FBXW7 established a direct mechanism for RICTOR proteasomal turnover and linked PI3K/Akt-mediated GSK3 inhibition to mTORC2 stabilization.

    Evidence In vitro GSK3 kinase assay, T1695A mutagenesis, FBXW7-RICTOR Co-IP, ubiquitination assay, mTORC2 activity measurement

    PMID:25897075

    Open questions at the time
    • Whether other E3 ligases also target RICTOR for degradation unknown
    • Quantitative contribution of this degron to RICTOR half-life in different tissues not measured
  12. 2015 High

    Discovery that glucose-driven acetylation of RICTOR maintains mTORC2 activity independently of receptor tyrosine kinase signaling revealed a metabolic mechanism sustaining mTORC2 in nutrient-replete conditions and explained therapy resistance in glioblastoma.

    Evidence Acetylation assays in cell lines, mouse tumors, and clinical GBM samples; glucose/acetate manipulation; mTORC2 activity readouts

    PMID:26170313

    Open questions at the time
    • Specific acetyltransferase and deacetylase responsible not identified
    • Acetylation site(s) on RICTOR not mapped
  13. 2017 High

    B cell-specific RICTOR knockout revealed that mTORC2 controls BCR signaling through ezrin dephosphorylation and actin reorganization, providing a cell-type-specific mechanism linking RICTOR to immune receptor function.

    Evidence Conditional B cell Rictor KO mice, F-actin staining, BCR clustering imaging, phospho-Western, latrunculin rescue

    PMID:28821013

    Open questions at the time
    • Phosphatase mediating ezrin dephosphorylation downstream of RICTOR not identified
    • Whether this mechanism operates in T cells or other immune cells unknown
  14. 2020 High

    Identification of USP9X as the deubiquitinase removing Lys63-linked ubiquitin chains from RICTOR to promote mTORC2 assembly provided a growth factor-regulated positive mechanism complementing the GSK3/FBXW7 degradation pathway.

    Evidence Reciprocal Co-IP, Lys63-specific ubiquitin linkage analysis, USP9X knockdown/overexpression, in vivo mouse validation

    PMID:33378666

    Open questions at the time
    • E3 ligase that adds Lys63-linked chains to RICTOR not identified
    • Whether USP9X activity is directly regulated by growth factor receptor signaling or via intermediaries unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structural model of the RICTOR-SIN1 interface within mTORC2, the acetyltransferase/deacetylase pair controlling RICTOR acetylation, and the mechanistic basis for RICTOR's mTOR kinase-independent regulation of Rac/Cdc42 remain to be determined.
  • No atomic-resolution structure of full-length RICTOR or the RICTOR-SIN1 interface
  • Acetyltransferase and deacetylase for RICTOR not identified
  • Mechanism linking RICTOR to Rac/Cdc42 activation independent of mTOR kinase not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 3
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 1
Partners
CUL1FBXW7ILKMAPKAP1MLST8MTORPRR5USP9X
Complex memberships
Rictor-Cullin-1 E3 ligase complexmTORC2

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 RICTOR (rapamycin-insensitive companion of mTOR) was identified as a novel binding partner of mTOR, defining a distinct complex (mTORC2) that contains GβL but not raptor, is insensitive to FKBP12-rapamycin, does not regulate S6K1, but modulates phosphorylation of PKCα and the actin cytoskeleton. Rictor shares homology with yeast AVO3p, which is part of a rapamycin-insensitive TOR complex that signals to the actin cytoskeleton through PKC1. Co-immunoprecipitation, mass spectrometry, siRNA knockdown, actin cytoskeleton assays, sequence homology Current biology : CB High 15268862
2005 The rictor-mTOR complex directly phosphorylates Akt/PKB on Ser473 in vitro, and rictor or mTOR knockdown inhibits Ser473 phosphorylation in Drosophila and human cells, facilitating subsequent Thr308 phosphorylation by PDK1. Rictor-mTOR functions as the elusive PDK2 for Akt hydrophobic motif phosphorylation. In vitro kinase assay with purified rictor-mTOR complex, RNAi knockdown in Drosophila and human cells, Western blot for phospho-Akt Science (New York, N.Y.) High 15718470
2005 The rictor-mTOR complex (but not raptor-mTOR) phosphorylates the hydrophobic motif (Thr389) of rapamycin-resistant S6K1 mutants lacking the C-terminal domain, demonstrating that rictor-mTOR can phosphorylate AGC kinase hydrophobic motifs in a TOR-signaling-motif-independent manner dependent on substrate structure. In vitro kinase assay comparing raptor-mTOR vs rictor-mTOR complexes on wild-type and mutant S6K1 substrates The Journal of biological chemistry High 15809305
2006 Genetic ablation of rictor in mice shows that mLST8 is required to maintain the rictor-mTOR interaction, and both mLST8 and rictor are required for hydrophobic motif phosphorylation of Akt/PKB (Ser473) and PKCα, but not S6K1. mTORC2 is required for insulin signaling to FOXO3 but not to TSC2 or GSK3β. Mouse knockout (rictor-null, mLST8-null, raptor-null), co-immunoprecipitation, Western blot for phosphorylation of downstream substrates Developmental cell High 17141160
2006 SIN1/MIP1 is an essential mTORC2 subunit; genetic ablation of sin1 abolishes Akt-Ser473 phosphorylation and disrupts rictor-mTOR interaction while maintaining Thr308 phosphorylation. Defective Ser473 phosphorylation selectively affects FoxO1/3a targets but not TSC2, GSK3, S6K, or 4E-BP1, demonstrating substrate-selective dependence on Rictor-SIN1-mTOR function. sin1 genetic knockout, co-immunoprecipitation, Western blot for phosphosubstrates, epistasis analysis Cell High 16962653
2007 Protor-1 and Protor-2 interact with Rictor and are components of mTORC2. Immunoprecipitation of Protor-1 or Protor-2 co-immunoprecipitates other mTORC2 subunits but not raptor. Detergents dissociate mTOR and mLST8 from a Protor-1/Sin1/Rictor complex. Rictor regulates Protor-1 expression levels, but Protor-1 is not required for assembly of other mTORC2 subunits. Co-immunoprecipitation, detergent fractionation, siRNA knockdown, Western blot The Biochemical journal High 17461779
2007 In Drosophila, rictor-null mutants show reduced Akt-Ser505 phosphorylation (equivalent to mammalian Ser473) and augmented FOXO-dependent apoptosis, while S6K-Thr398 phosphorylation and S6K-induced cell overgrowth are unaffected, establishing that rictor controls the Akt-FOXO axis but not the raptor-S6K axis in vivo. Drosophila rictor-null genetic analysis, phospho-Western blot, tissue hyperplasia assays Biochemical and biophysical research communications High 17462592
2009 S6K1, activated downstream of mTORC1, directly phosphorylates Rictor on Thr1135 in vitro and in vivo in a rapamycin-sensitive manner. This phosphorylation does not affect mTORC2 assembly, kinase activity toward Akt, or cellular localization of the complex, but cells expressing Rictor T1135A show increased mTORC2-dependent Akt phosphorylation and elevated FoxO1/3a and GSK3α/β phosphorylation, indicating S6K1-mediated phosphorylation of Rictor inhibits mTORC2/Akt signaling. In vitro kinase assay (S6K1 phosphorylating Rictor), phospho-specific antibody, rapamycin treatment, T1135A mutant rescue, co-immunoprecipitation for complex integrity Molecular and cellular biology High 19995915
2009 Rictor Thr1135 is phosphorylated by S6K1 in a rapamycin-sensitive manner, with the phosphorylated form binding 14-3-3 proteins, providing a mechanism for altered mTORC2 interactions. Phosphorylation at this site turns over rapidly and does not cause major changes in mTORC2 kinase activity per se. In vitro kinase assay, mass spectrometry identification of phosphorylation sites, 14-3-3 pull-down, rapamycin inhibition Oncogene High 19935711
2009 In C. elegans, Rictor/TORC2 regulates fat metabolism, growth, feeding, and life span; the fat and metabolic phenotypes are genetically dependent on akt-1, akt-2, and sgk-1, while life span, growth, and reproductive phenotypes are predominantly mediated by sgk-1, identifying SGK as an mTORC2 effector in vivo. Forward genetic screen for fat phenotypes, C. elegans rictor loss-of-function mutants, epistasis analysis with akt and sgk-1 mutants, rescue experiments Genes & development High 19240135
2009 In C. elegans, Rictor/TORC2-dependent fat, growth, and developmental phenotypes are mediated by SGK-1, not by AKT kinases or DAF-16/FOXO; a gain-of-function sgk-1 mutation suppresses Rictor mutant phenotypes, establishing SGK-1 as the primary downstream effector of TORC2 for metabolic and growth regulation. C. elegans rictor loss-of-function mutants, sgk-1 gain-of-function suppressor screen, genetic epistasis PLoS biology High 19260765
2008 Hsp70 physically associates with Rictor (identified by yeast two-hybrid and confirmed by co-immunoprecipitation and colocalization), and cells with antisense RNA targeting Hsp70 show impaired mTORC2 formation and reduced mTORC2 kinase activity toward Akt Ser473, without affecting mTORC1. Yeast two-hybrid, co-immunoprecipitation, colocalization, antisense knockdown, in vitro mTORC2 kinase assay Biochemical and biophysical research communications Medium 18505677
2010 Rictor interacts with Cullin-1 to form a ubiquitin E3 ligase complex (distinct from mTORC2) that promotes SGK1 ubiquitination and degradation. Rictor phosphorylation at Thr1135 by AGC kinases (Akt, S6K, SGK1) disrupts the Rictor-Cullin-1 interaction, impairing SGK1 ubiquitination and degradation as a feedback mechanism. Co-immunoprecipitation of Rictor-Cullin-1 complex, in vitro ubiquitination assay, phosphomimetic (T1135E) mutant, Rictor-/- MEFs measuring SGK1 levels Protein & cell Medium 21204013
2011 A single point mutation in Rictor (G934E), analogous to a C. elegans rictor mutation associated with elevated fat storage, prevents binding of Rictor to Sin1 and blocks mTORC2 assembly without affecting Protor binding. Substitution of Gly-934 with a charged amino acid is sufficient to disrupt the Rictor/Sin1 heterodimer and abolish mTORC2 Akt Ser473 phosphorylation and cell proliferation. Site-directed mutagenesis, co-immunoprecipitation of complex components, Western blot for Akt Ser473 phosphorylation, cell proliferation assay Oncogene High 21909137
2013 In neutrophil-like HL-60 cells, Rictor (but not Raptor or mSin1) depletion impairs actin polymerization, leading-edge establishment, and directional migration in response to chemoattractants. mTOR kinase activity and AKT phosphorylation are dispensable; instead, Rac and Cdc42 GTPases act as downstream effectors of Rictor to regulate actin assembly in an mTORC2- and mTOR kinase-independent manner. siRNA knockdown of Rictor vs. Raptor vs. mSin1, chemical mTOR inhibition, kinase-dead mutant expression, Rac/Cdc42 activity assays, actin polymerization assays, chemotaxis assays Molecular biology of the cell High 24006489
2012 EGF induces translocation and colocalization of Rictor with PKCζ; Rictor co-immunoprecipitates with PKCζ independently of the mTORC2 complex. Rictor knockdown inhibits EGF-induced PKCζ phosphorylation and translocation, as well as phosphorylation of the actin-binding protein cofilin, and reduces breast cancer cell chemotaxis and metastasis. Co-immunoprecipitation, colocalization imaging, siRNA knockdown, phospho-Western blot, chemotaxis assay, xenograft metastasis model Cancer research Medium 20978191
2012 ILK physically interacts with Rictor (identified by co-immunoprecipitation) upon TGFβ-1 treatment; this ILK/Rictor complex is present in cancer cells but not normal cells. ILK inhibition suppresses TGFβ-1-induced Rictor expression and Thr1135 phosphorylation, Snail/Slug nuclear translocation, and EMT markers, demonstrating a requirement for ILK/Rictor interaction in TGFβ-1-induced EMT. Co-immunoprecipitation, siRNA knockdown of ILK or Rictor, ILK kinase inhibitor, Western blot for phospho-Rictor Thr1135, EMT marker assessment Oncogene Medium 22310280
2013 Rictor associates with FBXW7 to form an E3 ligase complex biochemically distinct from mTORC2 that regulates ubiquitination and degradation of c-Myc and cyclin E. Rictor knockdown decreases ubiquitination of c-Myc and cyclin E; FBXW7 knockout blunts rictor's effects, establishing a rictor-FBXW7 axis for oncogene degradation. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown of Rictor, FBXW7 knockout, Western blot for c-Myc/cyclin E levels Biochemical and biophysical research communications Medium 22285861
2013 Brain-specific or Purkinje cell-specific conditional deletion of Rictor reduces Akt, PKC, and SGK1 phosphorylation (without affecting mTORC1), decreases expression of multiple PKC isoforms, reduces activation of downstream PKC substrates GAP-43 and MARCKS, and results in smaller neurons with defective morphology and function, linking mTORC2-Rictor to PKC-mediated cytoskeletal organization in neurons. Conditional Cre/loxP knockout in brain/Purkinje cells, Western blot for Akt/PKC/SGK1 phosphorylation, immunohistochemistry, neuronal morphology analysis The Journal of cell biology High 23569215
2015 Rictor undergoes proteasomal degradation via an FBXW7-mediated ubiquitination mechanism that requires GSK3-dependent phosphorylation of Rictor at Thr-1695 within a CDC4 phospho-degron motif. GSK3 directly phosphorylates Thr-1695 in vitro; mutation of this site impairs Rictor-FBXW7 interaction and increases Rictor stability. PI3K/Akt-mediated suppression of GSK3 thus stabilizes Rictor and enhances mTORC2 activity. In vitro GSK3 kinase assay on Rictor, site-directed mutagenesis (T1695A), co-immunoprecipitation of FBXW7-Rictor, proteasome inhibitor treatment, ubiquitination assay, mTORC2 activity measurement The Journal of biological chemistry High 25897075
2015 Glucose or acetate promotes acetyl-CoA-dependent acetylation of Rictor, maintaining mTORC2 activity in an autoactivation loop even when upstream growth factor receptor signaling is inhibited, rendering glioblastoma cells resistant to EGFR-, PI3K-, or AKT-targeted therapies. Acetylation assays in cell lines, mouse tumor models, and clinical GBM samples; glucose/acetate deprivation; acetyl-CoA manipulation; mTORC2 activity assays Proceedings of the National Academy of Sciences of the United States of America High 26170313
2013 IKKα and IKKβ physically interact with Rictor (co-immunoprecipitation both endogenous and ectopic); the binding domain on Rictor was mapped to amino acids 999-1397. Chemical inhibition or siRNA knockdown of IKK reduces Akt Ser473 and PKCα phosphorylation and disrupts actin cytoskeleton; kinase-dead IKK interacts with Rictor and competes with mTOR, reducing mTORC2 assembly and activity. Co-immunoprecipitation, in vitro binding assay, IKK inhibitor, siRNA knockdown, kinase-dead IKK mutant, mTORC2 kinase activity assay Cellular signalling Medium 23872070
2014 A transmembrane protein (UT2/Upstream of mTORC2) physically interacts with and inhibits RICTOR in hematopoietic progenitor cells, reducing mTORC2 enzymatic activity and decreasing phosphorylation of AKT(S473), PKCα, and NDRG1 while increasing FOXO transcriptional activity. Modulating UT2 levels altered animal survival in a T-ALL model. Co-immunoprecipitation of UT2 with RICTOR, in vitro mTORC2 kinase activity assay, knockdown/overexpression of UT2, phospho-Western blot for mTORC2 substrates, T-ALL mouse model Stem cell reports Medium 25418727
2017 A small molecule (CID613034) identified by yeast two-hybrid screen specifically blocks the Rictor-mTOR protein-protein interaction, inhibiting mTORC2 kinase activity at submicromolar concentrations and selectively reducing phosphorylation of mTORC2 substrates (AKT Ser473, NDRG1 Thr346, PKCα Ser657) without affecting mTORC1 substrate S6K phosphorylation. An optimized analog JR-AB2-011 showed anti-GBM activity in xenograft models. High-throughput yeast two-hybrid screen, in vitro mTORC2 kinase assay, phospho-Western blot for selective substrates, GBM xenograft model PloS one High 28453552
2020 USP9X deubiquitinase removes Lys63-linked ubiquitin chains from RICTOR to promote its interaction with mTOR, thereby facilitating mTORC2 assembly and signaling. Growth factors regulate USP9X activity to stimulate mTORC2 assembly; this mechanism was validated in human cell lines and mice. Co-immunoprecipitation, ubiquitin linkage analysis (Lys63-specific), USP9X knockdown/overexpression, Western blot for mTORC2 assembly and Akt Ser473 phosphorylation, mouse validation Cell reports High 33378666
2018 PARP3 interacts with and ADP-ribosylates GSK3β, a positive regulator of Rictor ubiquitination and degradation; PARP3 loss leads to enhanced Rictor ubiquitination and reduced Rictor/mTORC2 signaling selectively in BRCA1-deficient cells. PARP3 catalytic activity is required, as a catalytic mutant cannot rescue the phenotype. Co-immunoprecipitation of PARP3-GSK3β, ubiquitination assay, CRISPR/nCas9 PARP3 knockout, catalytic mutant rescue, Western blot for mTORC2 signaling, in vivo tumorigenicity Cell death and differentiation Medium 30442946
2017 Rictor in B cells positively regulates BCR signaling by controlling actin reorganization via ezrin dephosphorylation. Rictor KO B cells show increased F-actin accumulation after BCR stimulation due to dysregulated ezrin phosphorylation, restricting BCR lateral movement and clustering, and reducing BCR signaling (decreased pBtk, increased pSHIP). Latrunculin-mediated actin depolymerization rescues BCR signaling defects. B cell-specific Rictor KO mice, F-actin staining, BCR clustering imaging, phospho-Western blot, pharmacological actin inhibition rescue experiment PLoS biology High 28821013
2005 In Saccharomyces cerevisiae, TSC11/AVO3 (the Rictor ortholog) is an essential component of TORC2 required for cell integrity; ts alleles show cell wall defects. Genetic analysis links Tsc11p function to a Pkc1p-independent mechanism through Avo1p and a Pkc1p-dependent mechanism through Avo2p and Slm1p, demonstrating functional connections among TORC2 components. Temperature-sensitive allele analysis, osmotic stabilizer rescue, dosage suppression screen, genetic epistasis with PKC1, AVO1, AVO2, SLM1 Current genetics Medium 15809876
2020 Rictor interacts with ABLIM1 and regulates its serine phosphorylation; Rictor knockdown suppresses cell migration and actin polymerization by reducing nuclear accumulation of MKL1 and inactivating SRF/MKL1-dependent transcription of Arp3 and c-Fos. ABLIM1 Ser214/Ser431 phosphorylation mediates actin polymerization and MKL1 signaling downstream of Rictor. Co-immunoprecipitation of Rictor-ABLIM1, CRISPR knockout of ABLIM1, phospho-site mutants (S214A/S431A), actin polymerization assays, MKL1 nuclear localization imaging, luciferase reporter for SRF/MKL1 activity International journal of biological sciences Medium 33061800
2015 Tspan8 forms a complex with integrin α3 and Rictor in glioma cells; knockdown of any of the three proteins inhibits U251MG glioma cell migration. Tspan8 knockdown prevents mTOR-rictor (mTORC2) assembly and reduces Akt Ser473 and PKCα phosphorylation, showing Tspan8 is required for mTORC2 activation. Co-immunoprecipitation of Tspan8-integrin α3-Rictor complex, siRNA knockdown of each component, mTORC2 kinase activity (phospho-Akt/PKCα), migration assay International journal of molecular sciences Low 25761241

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.) 5524 15718470
2004 Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Current biology : CB 2199 15268862
2006 Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Developmental cell 1202 17141160
2006 SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 1159 16962653
2007 Identification of Protor as a novel Rictor-binding component of mTOR complex-2. The Biochemical journal 357 17461779
2009 mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling. Molecular and cellular biology 352 19995915
2009 Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans. Genes & development 338 19240135
2018 Vascular Compartmentalization of Functional Hyperemia from the Synapse to the Pia. Neuron 191 29937277
2013 Ablation of the mTORC2 component rictor in brain or Purkinje cells affects size and neuron morphology. The Journal of cell biology 186 23569215
2009 Increased AKT S473 phosphorylation after mTORC1 inhibition is rictor dependent and does not predict tumor cell response to PI3K/mTOR inhibition. Molecular cancer therapeutics 178 19372546
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 141 24671993
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
2012 Role of the integrin-linked kinase (ILK)/Rictor complex in TGFβ-1-induced epithelial-mesenchymal transition (EMT). Oncogene 117 22310280
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 102 26170313
2014 Depletion of Rictor, an essential protein component of mTORC2, decreases male lifespan. Aging cell 94 25059582
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
2015 MicroRNA-15b/16 Enhances the Induction of Regulatory T Cells by Regulating the Expression of Rictor and mTOR. Journal of immunology (Baltimore, Md. : 1950) 86 26538392
2020 TELO2 induced progression of colorectal cancer by binding with RICTOR through mTORC2. Oncology reports 81 33416177
2016 Integrin-α10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma. Cancer discovery 76 27577794
2015 Rictor/mTORC2 signaling mediates TGFβ1-induced fibroblast activation and kidney fibrosis. Kidney international 76 25970154
2014 Rictor/mTORC2 protects against cisplatin-induced tubular cell death and acute kidney injury. Kidney international 74 24451322
2016 Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers. Cancer research 73 27197158
2017 Specific blockade of Rictor-mTOR association inhibits mTORC2 activity and is cytotoxic in glioblastoma. PloS one 68 28453552
2013 MiR-424/503-mediated Rictor upregulation promotes tumor progression. PloS one 68 24244675
2013 Requirement for Rictor in homeostasis and function of mature B lymphoid cells. Blood 64 23958952
2013 Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton. Molecular biology of the cell 64 24006489
2015 Rictor/mTORC2 pathway in oocytes regulates folliculogenesis, and its inactivation causes premature ovarian failure. The Journal of biological chemistry 63 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
2014 Using phylogenetically-informed annotation (PIA) to search for light-interacting genes in transcriptomes from non-model organisms. BMC bioinformatics 58 25407802
2017 RICTOR amplification identifies a subgroup in small cell lung cancer and predicts response to drugs targeting mTOR. Oncotarget 55 27863413
2018 Unmasking the impact of Rictor in cancer: novel insights of mTORC2 complex. Carcinogenesis 52 29955840
2010 Rictor regulates MMP-9 activity and invasion through Raf-1-MEK-ERK signaling pathway in glioma cells. Molecular carcinogenesis 51 21557327
2018 The role of RICTOR downstream of receptor tyrosine kinase in cancers. Molecular cancer 50 29455662
2007 Rapamycin regulates the phosphorylation of rictor. Biochemical and biophysical research communications 50 17707343
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 49 37730744
2017 Regulation of Osteoclast Growth and Fusion by mTOR/raptor and mTOR/rictor/Akt. Frontiers in cell and developmental biology 49 28573133
2018 MicroRNA-142-3p Induces Atherosclerosis-Associated Endothelial Cell Apoptosis by Directly Targeting Rictor. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 48 29949787
2014 Staphylococcus aureus glucose-induced biofilm accessory proteins, GbaAB, influence biofilm formation in a PIA-dependent manner. International journal of medical microbiology : IJMM 47 24836943
2012 Resveratrol-mediated downregulation of Rictor attenuates autophagic process and suppresses UV-induced skin carcinogenesis. Photochemistry and photobiology 47 22272775
2012 Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells. Biochemical and biophysical research communications 46 22285861
2016 Loss of Rictor with aging in osteoblasts promotes age-related bone loss. Cell death & disease 45 27735936
2016 Targeted Inhibition of Rictor/mTORC2 in Cancer Treatment: A New Era after Rapamycin. Current cancer drug targets 44 26563881
2012 Receptor-specific mechanisms regulate phosphorylation of AKT at Ser473: role of RICTOR in β1 integrin-mediated cell survival. PloS one 44 22384145
2012 Conditional astroglial Rictor overexpression induces malignant glioma in mice. PloS one 44 23077666
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
2008 Polymorphism Interaction Analysis (PIA): a method for investigating complex gene-gene interactions. BMC bioinformatics 37 18325117
2017 Inhibition of mTORC2 component RICTOR impairs tumor growth in pancreatic cancer models. Oncotarget 35 28445935
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 34 35238644
2015 Tetraspanin 8-rictor-integrin α3 complex is required for glioma cell migration. International journal of molecular sciences 34 25761241
2013 IKK interacts with rictor and regulates mTORC2. Cellular signalling 34 23872070
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 PARP3, a new therapeutic target to alter Rictor/mTORC2 signaling and tumor progression in BRCA1-associated cancers. Cell death and differentiation 32 30442946
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
2023 RBM45 reprograms lipid metabolism promoting hepatocellular carcinoma via Rictor and ACSL1/ACSL4. Oncogene 30 38040804
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
2013 The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells. PloS one 29 24086535
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 28 34916779
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
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
2018 Down-regulation of Rictor enhances cell sensitivity to PI3K inhibitor LY294002 by blocking mTORC2-medicated phosphorylation of Akt/PRAS40 in esophageal squamous cell carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 30119206
2017 Rictor/mammalian target of rapamycin complex 2 promotes macrophage activation and kidney fibrosis. The Journal of pathology 27 28585302
2015 RICTOR involvement in the PI3K/AKT pathway regulation in melanocytes and melanoma. Oncotarget 27 26356562
1997 Ganglionic axons in motor roots and pia mater. Progress in neurobiology 27 9247961
1993 Structural comparison and epitope analysis of outer-membrane protein PIA from strains of Neisseria gonorrhoeae with differing serovar specificities. Journal of general microbiology 27 7506294
2020 The role of RICTOR amplification in targeted therapy and drug resistance. Molecular medicine (Cambridge, Mass.) 26 32041519
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
2011 Alcohol-induced modulation of rictor and mTORC2 activity in C2C12 myoblasts. Alcoholism, clinical and experimental research 24 21438886
2018 Opposing Tumor-Promoting and -Suppressive Functions of Rictor/mTORC2 Signaling in Adult Glioma and Pediatric SHH Medulloblastoma. Cell reports 23 29996106
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 23 30004239
2022 LncRNA KCNQ1OT1 promotes osteogenic differentiation via miR-205-5p/RICTOR axis. Experimental cell research 21 35341776
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
2011 Integrity of mTORC2 is dependent on the rictor Gly-934 site. Oncogene 21 21909137
2021 mTOR-Rictor-EGFR axis in oncogenesis and diagnosis of glioblastoma multiforme. Molecular biology reports 20 34132942
2018 Loss of Rictor in Monocyte/Macrophages Suppresses Their Proliferation and Viability Reducing Atherosclerosis in LDLR Null Mice. Frontiers in immunology 20 29487597
2020 Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma. International journal of biological sciences 19 33061800
2021 Vimentin loss promotes cancer proliferation through up-regulating Rictor/AKT/β-catenin signaling pathway. Experimental cell research 18 34052237
2018 Rictor Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Suppressing Autophagy and Regulating MAPK Signaling. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 18 29550823
2014 Critical roles for Rictor/Sin1 complexes in interferon-dependent gene transcription and generation of antiproliferative responses. The Journal of biological chemistry 18 24469448
2023 The Ka /Ks and πa /πs Ratios under Different Models of Gametophytic and Sporophytic Selection. Genome biology and evolution 17 37561000
2016 Purification and Evaluation of Polysaccharide Intercellular Adhesion (PIA) Antigen from Staphylococcus epidermidis. Current microbiology 17 27460584
2011 mTOR-rictor is the Ser473 kinase for AKT1 in mouse one-cell stage embryos. Molecular and cellular biochemistry 17 22057724
2019 Streptomyces-derived actinomycin D inhibits biofilm formation via downregulating ica locus and decreasing production of PIA in Staphylococcus epidermidis. Journal of applied microbiology 16 31808241
2014 Transmembrane Inhibitor of RICTOR/mTORC2 in Hematopoietic Progenitors. Stem cell reports 16 25418727
2010 Phosphorylation of Rictor at Thr1135 impairs the Rictor/Cullin-1 complex to ubiquitinate SGK1. Protein & cell 16 21204013