Affinage

RPTOR

Regulatory-associated protein of mTOR · UniProt Q8N122

Length
1335 aa
Mass
149.0 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPTOR (Raptor) is the defining scaffolding subunit of mTOR complex 1 (mTORC1), forming a stoichiometric complex with mTOR that couples nutrient and growth signals to control of cell size, translation, and proliferation (PMID:12150925, PMID:12150926). Its central molecular function is substrate recruitment: Raptor binds the TOS motifs of S6K1 and 4E-BP1 and presents them to the mTOR kinase domain, such that TOS-motif mutations abolish Raptor binding and mTOR-catalyzed phosphorylation (PMID:12604610, PMID:12747827); it likewise scaffolds direct phosphorylation of IRS-1 via the IRS-1 SAIN domain and of SGK1, defining the substrate repertoire of mTORC1 and a negative-feedback loop on PI3K/Akt signaling (PMID:16354680, PMID:19561084, PMID:18570873). Complex assembly is stabilized by mLST8/GβL and is the target of rapamycin, which acts through FKBP12 to dissociate Raptor from mTOR without altering intrinsic kinase activity (PMID:12718876, PMID:15066126). Raptor is the principal hub for upstream signal integration: amino acids and glucose promote Raptor–Rag GTPase interaction that drives lysosomal recruitment of mTORC1, gated positively by OGT-mediated O-GlcNAcylation at Thr700 and EP300-mediated acetylation, and negatively by AMPK phosphorylation (Ser722/Ser792) that recruits 14-3-3 and by NLK phosphorylation (Ser863) that disrupts Rag binding (PMID:18497260, PMID:37541260, PMID:32561715, PMID:18439900, PMID:26588989). A dense array of kinases converges on Raptor to tune mTORC1 activity—RSK1/2, ERK1/2, CDK1, GSK3, ULK1, ICK, PKA, and TBK1—integrating MAPK, mitotic, autophagic, GPCR, and innate-immune inputs (PMID:18722121, PMID:21071439, PMID:20169205, PMID:21460630, PMID:22356909, PMID:31112131, PMID:31530866), while its abundance is governed by competing ubiquitination (DDB1-CUL4, VHL) and deubiquitination/stabilization (UCH-L1, USP9X) (PMID:23297343, PMID:34290272, PMID:28341829). Genetic ablation of Raptor in mice is embryonic-lethal, establishing mTORC1/Raptor as essential for early development (PMID:17141160). Beyond its mTOR-bound role, free Raptor scaffolds PHLPP2 stabilization to restrain hepatic Akt and lipogenesis, an mTOR-kinase-independent function (PMID:26743335).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2002 High

    Established the existence and identity of Raptor as an mTOR-associated protein required for nutrient signaling and cell size, defining the founding subunit of what became mTORC1.

    Evidence Co-IP, mass spectrometry, RNAi, and cell-size assays in mammalian cells

    PMID:12150925 PMID:12150926

    Open questions at the time
    • Did not resolve how Raptor mechanistically links mTOR to specific substrates
    • Stoichiometry and structural basis of the association unresolved
  2. 2003 High

    Defined the molecular basis of substrate recruitment, showing Raptor binds the TOS motif of S6K1 and 4E-BP1 to present them to mTOR, settling Raptor's role as a substrate-presenting scaffold.

    Evidence Co-IP, TOS-motif point mutants, in vitro kinase assays in mammalian cells

    PMID:12604610 PMID:12747827

    Open questions at the time
    • Did not address how other substrates lacking canonical TOS motifs are recognized
    • Structural geometry of substrate delivery to the kinase domain unknown
  3. 2003 High

    Showed that mLST8/GβL stabilizes the Raptor–mTOR association and renders complex regulation by nutrients and rapamycin operative, integrating a third subunit into mTORC1.

    Evidence Co-IP, in vitro kinase assay, RNAi in mammalian cells

    PMID:12718876

    Open questions at the time
    • Quantitative contribution of mLST8 versus Raptor to substrate phosphorylation not separated
    • Later shown dispensable for mTORC1 signaling in vivo (#10)
  4. 2004 High

    Distinguished Raptor-containing mTORC1 from Rictor-containing mTORC2, demonstrating Raptor specifies the rapamycin-sensitive, S6K1-directed branch of mTOR signaling.

    Evidence Reciprocal Co-IP, mass spectrometry, RNAi, immunofluorescence

    PMID:15268862

    Open questions at the time
    • Did not define substrate-recognition rules separating the two complexes beyond TOS dependence
  5. 2004 High

    Resolved the mechanism of rapamycin action, showing FKBP12–rapamycin dissociates Raptor from mTOR rather than directly inhibiting catalysis, explaining substrate uncoupling.

    Evidence Co-IP and direct in vitro binding/kinase assays

    PMID:15066126

    Open questions at the time
    • Did not explain rapamycin-resistant residual mTORC1 outputs
    • In vivo restraint of complex assembly by FKBP12 addressed only later (#17)
  6. 2006 High

    Identified IRS-1 and SGK1 as direct Raptor-scaffolded mTORC1 substrates, extending the substrate repertoire and revealing a feedback loop onto PI3K/Akt.

    Evidence Co-IP, RNAi, in vitro kinase and phospho-specific immunoblot in mammalian cells

    PMID:16354680 PMID:18570873

    Open questions at the time
    • Did not map the IRS-1 docking surface (resolved in 2009, #18)
    • Physiological balance of feedback versus forward signaling not quantified
  7. 2006 High

    Demonstrated genetic essentiality, showing Raptor-null mice die in early embryogenesis while mLST8 is dispensable for mTORC1, separating the two subunits' in vivo roles.

    Evidence Conditional/constitutive knockout mice with signaling readouts

    PMID:17141160

    Open questions at the time
    • Tissue-specific developmental requirements not dissected here
  8. 2007 Medium

    Provided the first structural framing of how Raptor/KOG1 positions its WD40 domain near the TOR kinase, supporting a physical substrate-delivery model.

    Evidence Single-particle electron microscopy of the yeast TOR1–KOG1 complex at 25 Å

    PMID:17679098

    Open questions at the time
    • Low resolution and yeast ortholog; no mutagenesis validation
    • Substrate-bound state not captured
  9. 2008 High

    Identified Raptor as the convergence point for energy stress, showing AMPK phosphorylation of Ser722/Ser792 recruits 14-3-3 to inhibit mTORC1, linking AMPK to direct mTORC1 suppression.

    Evidence In vitro kinase, phospho-mutant rescue, 14-3-3 Co-IP, RNAi

    PMID:18439900

    Open questions at the time
    • Mechanism by which 14-3-3 binding inhibits the complex not structurally defined
    • In vivo requirement confirmed only later (#39)
  10. 2008 High

    Established Raptor as the amino-acid sensing interface, showing GTP-loaded Rag GTPases bind Raptor to relocalize mTORC1 to lysosomes without directly stimulating kinase activity.

    Evidence Co-IP, dominant-active/negative Rag constructs, immunofluorescence, RNAi

    PMID:18497260

    Open questions at the time
    • How relocalization activates kinase activity not resolved here
    • Modifications gating Raptor–Rag binding identified only later (#30, #41)
  11. 2008 High

    Connected the Ras/MAPK pathway to mTORC1 by showing RSK1/2 directly phosphorylate Raptor at conserved RXRXXS/T sites to promote kinase activity.

    Evidence In vitro kinase, MS site mapping, mutagenesis, RNAi, oncogenic Ras/MEK constructs

    PMID:18722121

    Open questions at the time
    • Mechanism by which these phosphosites increase activity unknown
    • Overlap with ERK sites (#21) not fully deconvolved
  12. 2009 High

    Mapped insulin-driven Raptor phosphorylation hierarchy (Ser863 as master switch for Ser855/Ser859), defining how growth-factor signaling tunes mTORC1 kinase output.

    Evidence MS site mapping, phospho-antibodies, mutagenesis, in vitro kinase, Rheb overexpression

    PMID:19864431

    Open questions at the time
    • Did not identify all kinases for each site (later: ERK, ULK1, GSK3, NLK)
    • Structural consequence of multisite phosphorylation unresolved
  13. 2010 High

    Identified ERK1/2 and CDK1 as additional direct Raptor kinases, integrating MAPK and mitotic signals into mTORC1 control of translation and cell-cycle progression.

    Evidence Co-IP, in vitro kinase, MS site mapping, phospho-mutant cell-cycle analysis

    PMID:20169205 PMID:20439490 PMID:21071439

    Open questions at the time
    • Functional integration of overlapping ERK/RSK/CDK1 sites on Ser696/Ser863 not unified
    • Mitotic IRES-translation mechanism only partially defined
  14. 2011 High

    Revealed an autophagy feedback arm, showing ULK1 phosphorylates Raptor to reduce its 4E-BP1 binding without disrupting complex integrity.

    Evidence In vitro kinase, substrate-docking Co-IP, shRNA epistasis

    PMID:21460630

    Open questions at the time
    • Whether ULK1 phosphorylation impairs all substrates or selectively 4E-BP1 unclear
  15. 2012 High

    Added ICK as a Raptor kinase whose Thr908 phosphorylation is required for insulin/Rheb-driven mTORC1 activation, broadening the activating-kinase set.

    Evidence In vitro kinase, MS mapping, T908A mutagenesis, Co-IP

    PMID:22356909

    Open questions at the time
    • Mechanism by which Thr908 enables Rheb-driven activation unknown
    • Limited in vivo validation
  16. 2015 High

    Demonstrated multiple stress/nutrient kinases (GSK3, NLK) phosphorylate Ser859/Ser863 to control Raptor's mTOR and Rag interactions, mechanistically separating complex integrity from lysosomal recruitment.

    Evidence Co-IP, mutagenesis, shRNA/knockout, knock-in cells, immunofluorescence

    PMID:26348909 PMID:26588989

    Open questions at the time
    • Crosstalk and hierarchy among kinases targeting the same Raptor residues unresolved
  17. 2015 High

    Showed a conserved starvation response in which Snf1/AMPK phosphorylation drives Kog1/Raptor condensation and TORC1 disassembly, establishing phase-separation-like hysteresis in TORC1 reactivation.

    Evidence Yeast genetics, live-cell imaging, phospho-mutants, TORC1 activity assays

    PMID:26439012

    Open questions at the time
    • Whether mammalian Raptor undergoes analogous condensation untested here
  18. 2016 Medium

    Uncovered an mTOR-independent scaffolding role, showing free Raptor stabilizes PHLPP2 to restrain hepatic Akt and lipogenesis.

    Evidence Hepatocyte-specific Raptor knockout mice, Co-IP, PHLPP2 degradation assays

    PMID:26743335

    Open questions at the time
    • Single lab; structural basis of Raptor–PHLPP2 interaction undefined
    • Generality beyond liver unknown
  19. 2019 Medium

    Extended the kinase network to GPCR/PKA, innate-immune TBK1, and RAS-pathway SHOC2 competition, defining additional physiological contexts that suppress mTORC1 through Raptor.

    Evidence In vitro kinase, phospho-mutant rescue, competitive Co-IP, autophagy/ubiquitination assays

    PMID:30865892 PMID:31112131 PMID:31530866

    Open questions at the time
    • TBK1 (#36) and SHOC2 (#35) lack extensive in vivo validation
    • Integration of these inputs with the dominant nutrient pathway unclear
  20. 2020 High

    Defined acetyl-CoA-driven EP300 acetylation of Raptor as a metabolic switch coupling leucine and peroxisomal β-oxidation to mTORC1 activation and autophagy suppression.

    Evidence AcCoA/EP300 pharmacology, acetylation and autophagy assays, Acox1 knockout mice

    PMID:32561715 PMID:32687428

    Open questions at the time
    • Acetylated residue(s) and structural effect on the complex not fully mapped
  21. 2020 High

    Confirmed the physiological requirement of Raptor Ser722/Ser792 phosphorylation, showing knock-in mice resist metformin-driven mTORC1 inhibition, validating AMPK→Raptor signaling in vivo.

    Evidence Raptor S722A/S792A knock-in mice, primary hepatocytes, RNA-seq

    PMID:32912901

    Open questions at the time
    • Relative contribution of Raptor versus TSC2 phosphorylation not fully isolated
  22. 2021 Medium

    Identified VHL as a ubiquitin ligase that degrades Raptor to suppress mTORC1, adding tumor-suppressor control over Raptor abundance.

    Evidence Co-IP, ubiquitination assay, VHL gain/loss, C. elegans vhl-1 genetics

    PMID:34290272

    Open questions at the time
    • Direct versus indirect ubiquitination by VHL not fully distinguished
    • Single lab
  23. 2023 High

    Showed glucose-driven OGT O-GlcNAcylation of Raptor Thr700 promotes Raptor–Rag binding and lysosomal mTOR recruitment, and that AMPK phosphorylation antagonizes this modification, unifying nutrient and energy inputs at the Rag interface.

    Evidence O-GlcNAc proteomics, T700A mutagenesis, Co-IP, lysosomal fractionation, imaging, OGT inhibition

    PMID:37541260

    Open questions at the time
    • Structural basis of how Thr700 modification alters Rag binding unresolved
    • Crosstalk hierarchy with acetylation and phosphorylation not fully integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dense, overlapping array of Raptor modifications (phosphorylation, acetylation, O-GlcNAcylation, ubiquitination) is hierarchically integrated into a single quantitative mTORC1 activity setpoint, and the high-resolution structural geometry of substrate delivery, remain unresolved.
  • No unified model reconciling competing modifications at shared residues (e.g., Ser863, Ser792)
  • No high-resolution structure of human Raptor presenting a substrate to the mTOR kinase domain
  • Whether mTOR-independent scaffolding roles generalize beyond liver

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 5
Localization
GO:0005764 lysosome 3 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-9612973 Autophagy 5 R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2
Partners
AKT1S1EIF4EBP1IRS1MLST8MTORRPS6KB1RRAGASHOC2
Complex memberships
mTORC1

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Raptor forms a stoichiometric complex with mTOR; this association negatively regulates mTOR kinase activity under nutrient deprivation, while raptor is required for nutrient-stimulated signaling to S6K1, maintenance of cell size, and mTOR protein expression. Co-immunoprecipitation, mass spectrometry, RNAi knockdown, cell size measurements Cell High 12150925 12150926
2002 Raptor binds 4EBP1 and p70S6K and is required as a scaffold for mTOR-catalyzed phosphorylation of 4EBP1 in vitro; partial RNAi knockdown of raptor reduces mTOR-catalyzed 4EBP1 phosphorylation, and C. elegans raptor RNAi phenocopies Ce-TOR inactivation. In vitro kinase assay, Co-immunoprecipitation, RNAi in mammalian cells and C. elegans Cell High 12150926
2003 Raptor binds the TOS (TOR signaling) motif of p70S6K and 4EBP1; a point mutation in the 4EBP1 TOS motif abolishes raptor binding and eliminates mTOR-catalyzed 4EBP1 phosphorylation in vitro and in vivo, demonstrating raptor as the substrate-recruiting scaffold. Co-immunoprecipitation, site-directed mutagenesis, in vitro kinase assay, cell size measurement The Journal of biological chemistry High 12604610 12747827
2003 GbetaL (mLST8) binds the mTOR kinase domain and stabilizes the raptor–mTOR interaction; GbetaL stimulates mTOR kinase activity toward S6K1 and 4E-BP1, an effect reversed by stable raptor–mTOR association; nutrients and rapamycin regulate mTOR–raptor association only in complexes also containing GbetaL. Co-immunoprecipitation, in vitro kinase assay, RNAi, cell size measurement Molecular cell High 12718876
2004 Rictor defines a second mTOR complex (mTORC2) that does not contain raptor and is rapamycin-insensitive; raptor-containing mTORC1 regulates S6K1 while rictor-containing mTORC2 modulates PKCα phosphorylation and the actin cytoskeleton. Co-immunoprecipitation, mass spectrometry, RNAi, immunofluorescence Current biology : CB High 15268862
2004 Rapamycin/FKBP12 complex inhibits mTOR function at least in part by dissociating raptor from mTOR both in vivo and directly in vitro; this dissociation uncouples mTOR from raptor-dependent substrates without altering intrinsic mTOR catalytic activity. Co-immunoprecipitation, in vitro binding assay, in vitro kinase assay Genes to cells : devoted to molecular & cellular mechanisms High 15066126
2005 The raptor–mTOR complex selectively phosphorylates rapamycin-sensitive forms of S6K1, while the rictor–mTOR complex phosphorylates rapamycin-resistant S6K1 mutants lacking the C-terminal domain; TOS motif-independent recognition is required for rictor-mTOR-mediated phosphorylation. In vitro kinase assay, Co-immunoprecipitation, mutant S6K1 constructs The Journal of biological chemistry High 15809305
2005 Redox state regulates the raptor–mTOR complex: oxidizing agents increase S6K1 phosphorylation and make it nutrient-insensitive, while the reducing agent BAL stabilizes mTOR–raptor interaction (mimicking nutrient deprivation) and inhibits S6K1 phosphorylation. Co-immunoprecipitation, immunoblot, pharmacological redox manipulation The Journal of biological chemistry Medium 16183647
2006 Raptor-dependent mTOR directly phosphorylates IRS-1 at Ser636/639; raptor binds IRS-1 directly and serves as a scaffold for this phosphorylation, providing a mechanism for mTOR-mediated negative feedback on PI3K/Akt signaling. Co-immunoprecipitation, RNAi knockdown, phospho-specific immunoblot, in vitro kinase assay Molecular and cellular biology High 16354680 19561084
2006 Raptor is ubiquitinated by the DDB1-CUL4 ubiquitin ligase complex; the deubiquitylase UCH-L1 disrupts this DDB1-CUL4–raptor complex, counteracts raptor ubiquitination, and leads to mTORC1 dissolution with secondary mTORC2 increase. Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, Uchl1 transgenic and knockout mice Molecular and cellular biology High 23297343
2006 Mice lacking raptor die early in embryonic development, establishing that mTORC1/raptor function is essential for early development; mLST8 is required only for mTORC2 (rictor-mTOR) signaling to Akt and PKCα, not for raptor-mTOR signaling to S6K1. Conditional gene knockout mice, immunoprecipitation, immunoblot Developmental cell High 17141160
2007 Electron microscopy reconstruction revealed that yeast TOR1 N-terminal HEAT repeats form a curved tubular domain that associates with the C-terminal WD40 domain of KOG1/Raptor; the N terminus of KOG1 is proximal to the TOR kinase domain, supporting a substrate-delivery model. Single-particle electron microscopy, 3D reconstruction at 25 Å resolution Molecular cell Medium 17679098
2008 AMPK directly phosphorylates raptor on Ser722 and Ser792 under energy stress; this phosphorylation induces 14-3-3 binding to raptor and is required for mTORC1 inhibition and cell-cycle arrest induced by energy stress. In vitro kinase assay, phospho-specific antibodies, Co-immunoprecipitation of 14-3-3, RNAi, phospho-mutant rescue experiments Molecular cell High 18439900
2008 The Rag GTPases interact with mTORC1 in an amino-acid-sensitive manner through raptor; GTP-loaded Rag promotes mTORC1 lysosomal/intracellular relocalization to activate mTOR without directly stimulating mTOR kinase activity. Co-immunoprecipitation, dominant-active/dominant-negative Rag constructs, immunofluorescence localization, RNAi Science (New York, N.Y.) High 18497260
2008 RSK1/2, activated by the Ras/MAPK pathway, directly phosphorylate raptor on conserved RXRXXpS/T motifs in an evolutionarily conserved region; raptor phosphorylation-deficient mutants show reduced mTOR kinase activity, linking MAPK pathway to mTORC1 activation. In vitro kinase assay, RNAi, quantitative mass spectrometry, site-directed mutagenesis, oncogenic Ras/MEK constructs Current biology : CB High 18722121
2008 mTOR–raptor complex phosphorylates SGK1 at S422; raptor shRNA impairs mTOR-driven SGK1 activation (but not Akt), and mTOR/raptor/SGK1 complexes are detected in cells, implicating SGK1 as a direct mTORC1 substrate that mediates cytoplasmic p27 mislocalization. In vitro kinase assay, Co-immunoprecipitation, shRNA knockdown, phospho-specific immunoblot Molecular cell High 18570873
2008 Raptor is required for Akt-induced NF-κB activation downstream of mTOR; mTOR–raptor complex interacts with and stimulates IKK; rapamycin suppresses IKK activity possibly via raptor–mTOR dissociation. RNAi knockdown, Co-immunoprecipitation, IKK kinase assay, pharmacological inhibition Genes & development Medium 18519641
2008 FKBP12 deficiency in mouse brain increases basal mTOR phosphorylation and mTOR–Raptor interactions along with enhanced S6K phosphorylation, demonstrating that FKBP12 normally restrains mTOR–Raptor complex assembly. Brain-specific Fkbp12 conditional knockout mice, Co-immunoprecipitation, immunoblot Neuron Medium 19081378
2009 Raptor binds the SAIN domain of IRS-1 and this interaction is required for mTOR-mediated phosphorylation of IRS-1 at Ser-636/639; IRS-1 lacking the SAIN domain does not interact with raptor, is not phosphorylated at these sites, and has enhanced PI3K association. Co-immunoprecipitation, deletion mutant constructs, RNAi, phospho-specific immunoblot The Journal of biological chemistry Medium 19561084
2009 Raptor Ser863 is phosphorylated in response to insulin via the canonical PI3K/TSC/Rheb/mTORC1 pathway in a rapamycin-sensitive manner; Ser863 phosphorylation is a hierarchical master switch required for phosphorylation at Ser859 and Ser855; multisite phosphorylation-deficient raptor shows reduced in vitro mTORC1 kinase activity toward 4EBP1. Tandem mass spectrometry, phospho-specific antibody generation, site-directed mutagenesis, in vitro kinase assay, Rheb overexpression The Journal of biological chemistry High 19864431
2009 Hsp90 co-immunoprecipitates with raptor; geldanamycin disrupts Hsp90–raptor association (without affecting raptor–mTOR binding) and suppresses mTOR-mediated phosphorylation of S6K and 4E-BP1, indicating Hsp90 facilitates mTOR/raptor complex activity through raptor binding. Co-immunoprecipitation, pharmacological inhibition, immunoblot Journal of biochemistry Medium 16428328 19586661
2010 ERK1/2 interact with raptor and directly phosphorylate it on Ser8, Ser696, and Ser863 in response to Ras/MAPK activation; phosphorylation-deficient raptor alleles reduce mTORC1 activity and 4E-BP1 phosphorylation. Co-immunoprecipitation, in vitro kinase assay, mass spectrometry, phospho-specific antibodies, site-directed mutagenesis The Journal of biological chemistry High 21071439
2010 CDC2/CDK1 (cdc2) phosphorylates raptor on Ser696 and Thr706 during mitosis; Cyclin B co-immunoprecipitates with raptor in mitotic cells, and these mitotic phosphorylation events regulate mTORC1 during cell division. Tandem mass spectrometry, phospho-specific antibodies, site-directed mutagenesis, Co-immunoprecipitation, cell synchronization PloS one High 20169205
2010 Mitotic phosphorylation of raptor (by CDK1 and GSK3 pathways) facilitates G2/M cell cycle transit; phosphorylation-deficient raptor mutants cause G2/M delay while raptor depletion causes G1 accumulation; mitotic raptor promotes IRES-dependent mRNA translation. Phosphopeptide mapping, site-directed mutagenesis, cell cycle analysis, dominant-negative/constitutive kinase constructs Molecular and cellular biology Medium 20439490
2011 ULK1 phosphorylates raptor at multiple sites in vivo and in vitro (prominently Ser855 and Ser859, with moderate Ser792); ULK1-mediated raptor phosphorylation reduces the ability of raptor to bind substrate 4E-BP1 without disrupting mTORC1 complex integrity, providing a negative feedback mechanism. In vitro kinase assay, phospho-specific antibodies, Co-immunoprecipitation, shRNA knockdown, overexpression Autophagy High 21460630
2011 Raptor and Rheb negatively regulate skeletal myogenic differentiation through suppression of IRS1; raptor or Rheb knockdown enhances C2C12 differentiation accompanied by increased Akt activation and elevated IRS1 levels, and IRS1 knockdown abolishes this enhancement. RNAi knockdown, overexpression, C2C12 differentiation assay, immunoblot epistasis The Journal of biological chemistry Medium 21852229
2012 ICK (intestinal cell kinase) phosphorylates raptor at Thr908 both in vitro and in vivo; Raptor T908A mutant markedly impairs mTORC1 activation by insulin or Rheb overexpression without disrupting mTORC1 complex integrity. In vitro kinase assay, mass spectrometry, phospho-specific antibody, site-directed mutagenesis, Co-immunoprecipitation The Journal of biological chemistry High 22356909
2013 FLIM-FRET in live cells confirmed direct physical interaction between mTOR and raptor in the cytoplasm and nucleus; amino acid withdrawal and re-addition (but not rapamycin) alter mTOR intracellular distribution. FRET-FLIM live-cell imaging, GFP/DsRed fusion proteins BMC cell biology Medium 23311891
2015 GSK3 phosphorylates raptor at Ser859; GSK3 inhibition or shRNA silencing reduces mTOR–raptor interaction and attenuates amino-acid-regulated mTORC1 signaling, increased autophagic flux, and reduced proliferation. Pharmacological inhibition, shRNA, phospho-specific antibody, Co-immunoprecipitation, site-directed mutagenesis (S859A) The Biochemical journal Medium 26348909
2015 Glucose starvation in budding yeast triggers Snf1/AMPK-dependent phosphorylation of Kog1/Raptor at Ser491/494, driving TORC1 disassembly and condensation of Kog1 into a single body near the vacuole; these bodies increase the TORC1 activation threshold (hysteresis) during prolonged starvation. Yeast genetics, live-cell fluorescence microscopy, phospho-mutant constructs, TORC1 activity assays eLife High 26439012
2015 NLK phosphorylates raptor on Ser863 in response to osmotic/oxidative stress; this phosphorylation disrupts raptor's interaction with Rag GTPases, inhibits mTORC1 lysosomal localization, and suppresses mTORC1 activation; Raptor S863A knock-in cells are defective in stress-induced mTORC1 inhibition. In vitro kinase assay, Co-immunoprecipitation, phospho-specific antibody, Nlk knockout and Raptor knock-in cells, immunofluorescence Genes & development High 26588989
2016 Free (mTORC1-independent) Raptor negatively regulates hepatic Akt activity and lipogenesis by stabilizing the Akt phosphatase PHLPP2, reducing its β-TrCP-mediated degradation; this reveals a scaffolding function of Raptor independent of mTOR kinase. Hepatocyte-specific Raptor knockout mice, overexpression constructs, Co-immunoprecipitation, immunoblot, liver lipid measurements Nature communications Medium 26743335
2017 The mTOR–Raptor–S6K1 axis regulates Runx2 expression through S6K1-mediated phosphorylation of estrogen receptor α, which binds DLX5 and augments Runx2 enhancer activity; heterozygous Raptor mutation in osteoblasts aggravates bone defects in Runx2+/− mice. Conditional knockout mice, immunoblot, chromatin immunoprecipitation, genetic epistasis (Raptor×Runx2 double mutant) Cell death and differentiation Medium 28686577
2017 USP9X deubiquitylase physically associates with Raptor in embryonic brains, opposes proteasomal degradation of Raptor, and thereby maintains Raptor protein levels and mTORC1 signaling in neural progenitors; loss of Usp9x phenocopies Raptor-null neurospheres in reducing mTORC1 activity. Co-immunoprecipitation from embryonic brain, USP9X loss- and gain-of-function in cultured cells and Nestin-Cre Usp9x mice, proteasome inhibition assay, EdU proliferation assay Scientific reports Medium 28341829
2019 PKA phosphorylates Raptor at Ser791 in response to Gαs-coupled GPCR activation, leading to decreased mTORC1 activity; Raptor S791A mutant partially rescues mTORC1 activity after PKA activation, and this pathway operates in multiple cell lines and mouse tissues. In vitro kinase assay, phospho-specific antibody, Raptor S791A site-directed mutagenesis, pharmacological GPCR agonists, immunoblot in mouse tissues eLife High 31112131
2019 SHOC2 (a RAS activator) competes with mTOR for Raptor binding; SHOC2–Raptor interaction inhibits mTORC1 and induces autophagy, while Raptor binding to SHOC2 blocks RAS-MAPK signaling; FBXW7-mediated ubiquitination of SHOC2 terminates this cross-talk. Co-immunoprecipitation, competitive binding assay, ubiquitination assay, autophagy flux assay, cell proliferation assay Cell reports Medium 30865892
2019 TBK1 phosphorylates Raptor at Ser877 in vitro and promotes Ser877 phosphorylation in cells in response to pathogen-associated molecules; phosphorylation at Ser877 inversely correlates with mTORC1 activity, and Raptor S877A mutant increases mTORC1 activity. In vitro kinase assay coupled with mass spectrometry, phospho-specific antibody, Raptor S877A site-directed mutagenesis, immunoblot Scientific reports Medium 31530866
2020 Leucine regulates autophagy via its metabolite acetyl-CoA: AcCoA promotes EP300-dependent acetylation of raptor, which activates mTORC1 and suppresses autophagy; leucine deprivation decreases raptor acetylation and causes mTORC1 inhibition predominantly through this mechanism. Pharmacological manipulation of AcCoA, EP300 inhibitor, Co-immunoprecipitation, raptor acetylation assay, autophagy flux assay in multiple cell lines and neurons Nature communications High 32561715
2020 Hepatic peroxisomal β-oxidation suppresses lipophagy via RPTOR acetylation and mTOR activation; ACOX1 deficiency decreases cytosolic acetyl-CoA, reduces RPTOR acetylation, inhibits mTORC1, and induces lipophagy. Liver-specific Acox1 knockout mice, acetylation assay, mTORC1 activity measurement, lipophagy quantification Autophagy Medium 32687428
2020 AMPK-mediated phosphorylation of both RAPTOR (Ser722/Ser792) and TSC2 is required for full mTORC1 inhibition by metformin in primary hepatocytes and intact liver; Raptor knock-in mice (S722A/S792A) show incomplete mTORC1 inhibition and an attenuated transcriptional response to metformin. Raptor Ser722A/Ser792A knock-in mice, primary hepatocyte cultures, immunoblot, RNA-seq Genes & development High 32912901
2021 VHL interacts with RAPTOR and promotes RAPTOR degradation through ubiquitination, thereby suppressing mTORC1 signaling; loss of VHL in ccRCC increases RAPTOR levels and mTORC1 hyperactivation, consistent with a conserved mechanism also observed in C. elegans vhl-1 mutants. Co-immunoprecipitation, ubiquitination assay, VHL overexpression/silencing, C. elegans vhl-1 genetic analysis, immunoblot Scientific reports Medium 34290272
2023 O-GlcNAcylation of Raptor at Thr700 by OGT (driven by glucose availability) facilitates Raptor–Rag GTPase interactions and promotes lysosomal translocation of mTOR, thereby activating mTORC1; AMPK-mediated phosphorylation of Raptor suppresses Raptor O-GlcNAcylation and inhibits Raptor–Rag interactions. O-GlcNAc proteomics, site-directed mutagenesis (T700A), Co-immunoprecipitation, lysosomal fractionation, immunofluorescence, OGT inhibition Molecular cell High 37541260

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular cell 3150 18439900
2002 mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 2448 12150925
2008 The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science (New York, N.Y.) 2230 18497260
2004 Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Current biology : CB 2206 15268862
2002 Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 1485 12150926
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 1207 17141160
2003 GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Molecular cell 771 12718876
2003 The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. The Journal of biological chemistry 549 12604610
2008 Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK. Genes & development 544 18519641
2008 Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell metabolism 408 19046571
2003 TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Current biology : CB 401 12747827
2013 T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming. Immunity 337 24315998
2006 Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Molecular and cellular biology 336 16354680
2008 Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Current biology : CB 271 18722121
2004 Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes to cells : devoted to molecular & cellular mechanisms 243 15066126
2008 mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation. Molecular cell 222 18570873
2010 ERK1/2 phosphorylate Raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1). The Journal of biological chemistry 218 21071439
2005 Redox regulation of the nutrient-sensitive raptor-mTOR pathway and complex. The Journal of biological chemistry 200 16183647
2008 Removal of FKBP12 enhances mTOR-Raptor interactions, LTP, memory, and perseverative/repetitive behavior. Neuron 183 19081378
2011 ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding. Autophagy 175 21460630
2009 Curcumin disrupts the Mammalian target of rapamycin-raptor complex. Cancer research 168 19176385
2009 Regulation of mTOR complex 1 (mTORC1) by raptor Ser863 and multisite phosphorylation. The Journal of biological chemistry 155 19864431
2022 N7-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis. Nature communications 151 35304469
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
2006 Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis. Molecular and cellular biology 139 16914728
2009 mTOR phosphorylated at S2448 binds to raptor and rictor. Amino acids 127 19145465
2003 RAPTOR: optimal protein threading by linear programming. Journal of bioinformatics and computational biology 127 15290783
2018 The role of raptor in the mechanical load-induced regulation of mTOR signaling, protein synthesis, and skeletal muscle hypertrophy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 125 30509128
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
2008 AMPK and Raptor: matching cell growth to energy supply. Molecular cell 114 18471972
2009 Keratins regulate protein biosynthesis through localization of GLUT1 and -3 upstream of AMP kinase and Raptor. The Journal of cell biology 109 19841136
2018 Inhibition of mTORC1 by lncRNA H19 via disrupting 4E-BP1/Raptor interaction in pituitary tumours. Nature communications 106 30397197
2020 Leucine regulates autophagy via acetylation of the mTORC1 component raptor. Nature communications 103 32561715
2017 Selective interference of mTORC1/RAPTOR protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism with Akt and autophagy induction. Osteoarthritis and cartilage 102 28888905
2016 Raptor/mTORC1 loss in adipocytes causes progressive lipodystrophy and fatty liver disease. Molecular metabolism 101 27257602
2004 Raptor and mTOR: subunits of a nutrient-sensitive complex. Current topics in microbiology and immunology 100 14560962
2007 Interferon-gamma induces human vascular smooth muscle cell proliferation and intimal expansion by phosphatidylinositol 3-kinase dependent mammalian target of rapamycin raptor complex 1 activation. Circulation research 99 17656678
2020 MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy. Cell death & disease 95 32814765
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
2010 Mitotic raptor promotes mTORC1 activity, G(2)/M cell cycle progression, and internal ribosome entry site-mediated mRNA translation. Molecular and cellular biology 87 20439490
2020 AMPK regulation of Raptor and TSC2 mediate metformin effects on transcriptional control of anabolism and inflammation. Genes & development 86 32912901
2015 Snf1/AMPK promotes the formation of Kog1/Raptor-bodies to increase the activation threshold of TORC1 in budding yeast. eLife 84 26439012
2019 GPCR signaling inhibits mTORC1 via PKA phosphorylation of Raptor. eLife 81 31112131
2017 Raptor regulates functional maturation of murine beta cells. Nature communications 77 28598424
2016 Inactivation of Regulatory-associated Protein of mTOR (Raptor)/Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling in Osteoclasts Increases Bone Mass by Inhibiting Osteoclast Differentiation in Mice. The Journal of biological chemistry 72 27879318
2016 Conditional Disruption of Raptor Reveals an Essential Role for mTORC1 in B Cell Development, Survival, and Metabolism. Journal of immunology (Baltimore, Md. : 1950) 71 27521345
2004 Raptor, a binding partner of target of rapamycin. Biochemical and biophysical research communications 70 14684181
2013 Ubiquitin hydrolase UCH-L1 destabilizes mTOR complex 1 by antagonizing DDB1-CUL4-mediated ubiquitination of raptor. Molecular and cellular biology 68 23297343
2007 Structure of TOR and its complex with KOG1. Molecular cell 66 17679098
2018 RAPTOR Controls Developmental Growth Transitions by Altering the Hormonal and Metabolic Balance. Plant physiology 65 29686055
2007 Raptor-rictor axis in TGFbeta-induced protein synthesis. Cellular signalling 60 18068336
2009 Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR. The Journal of biological chemistry 59 19561084
2010 Raptor is phosphorylated by cdc2 during mitosis. PloS one 57 20169205
2009 Activation of mTORC1 in two steps: Rheb-GTP activation of catalytic function and increased binding of substrates to raptor. Biochemical Society transactions 57 19143636
2016 mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2. Nature communications 56 26743335
2015 GSK3-mediated raptor phosphorylation supports amino-acid-dependent mTORC1-directed signalling. The Biochemical journal 56 26348909
2017 mTOR/Raptor signaling is critical for skeletogenesis in mice through the regulation of Runx2 expression. Cell death and differentiation 55 28686577
2013 mTOR direct interactions with Rheb-GTPase and raptor: sub-cellular localization using fluorescence lifetime imaging. BMC cell biology 54 23311891
2011 Phosphorylation of Raptor by p38beta participates in arsenite-induced mammalian target of rapamycin complex 1 (mTORC1) activation. The Journal of biological chemistry 53 21757713
2013 A role for Raptor phosphorylation in the mechanical activation of mTOR signaling. Cellular signalling 50 24239769
2017 Regulation of Osteoclast Growth and Fusion by mTOR/raptor and mTOR/rictor/Akt. Frontiers in cell and developmental biology 49 28573133
2015 Autophagy-related genes Raptor, Rictor, and Beclin1 expression and relationship with multidrug resistance in colorectal carcinoma. Human pathology 49 26363527
2023 O-GlcNAcylation of Raptor transduces glucose signals to mTORC1. Molecular cell 47 37541260
2006 Suppression of the mTOR-raptor signaling pathway by the inhibitor of heat shock protein 90 geldanamycin. Journal of biochemistry 46 16428328
2006 PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals. Cellular signalling 46 16837165
2015 NLK phosphorylates Raptor to mediate stress-induced mTORC1 inhibition. Genes & development 44 26588989
2013 Disruption of an hTERT-mTOR-RAPTOR protein complex by a phytochemical perillyl alcohol and rapamycin. Molecular and cellular biochemistry 44 23283642
2019 The FBXW7-SHOC2-Raptor Axis Controls the Cross-Talks between the RAS-ERK and mTORC1 Signaling Pathways. Cell reports 43 30865892
2004 Raptor: combining dual-shell representation, induced-fit simulation, and hydrophobicity scoring in receptor modeling: application toward the simulation of structurally diverse ligand sets. Journal of medicinal chemistry 41 15566288
2015 Evolutionary conservation of TORC1 components, TOR, Raptor, and LST8, between rice and yeast. Molecular genetics and genomics : MGG 40 25956502
2017 USP9X deubiquitylating enzyme maintains RAPTOR protein levels, mTORC1 signalling and proliferation in neural progenitors. Scientific reports 38 28341829
2017 The Glial Cell-Derived Neurotrophic Factor (GDNF)-responsive Phosphoprotein Landscape Identifies Raptor Phosphorylation Required for Spermatogonial Progenitor Cell Proliferation. Molecular & cellular proteomics : MCP 38 28408662
2012 Osmotic stress regulates mammalian target of rapamycin (mTOR) complex 1 via c-Jun N-terminal Kinase (JNK)-mediated Raptor protein phosphorylation. The Journal of biological chemistry 38 22493283
2022 Real age prediction from the transcriptome with RAPToR. Nature methods 36 35817937
2019 TBK1 Limits mTORC1 by Promoting Phosphorylation of Raptor Ser877. Scientific reports 36 31530866
2018 Raptor directs Sertoli cell cytoskeletal organization and polarity in the mouse testis. Biology of reproduction 36 29961810
2009 Distinct roles of the mTOR components Rictor and Raptor in MO7e megakaryocytic cells. European journal of haematology 36 19341427
2020 Raptor determines β-cell identity and plasticity independent of hyperglycemia in mice. Nature communications 35 32439909
2013 Platelet-derived growth factor-induced Akt phosphorylation requires mTOR/Rictor and phospholipase C-γ1, whereas S6 phosphorylation depends on mTOR/Raptor and phospholipase D. Cell communication and signaling : CCS 35 23311350
2005 LAS24/KOG1, a component of the TOR complex 1 (TORC1), is needed for resistance to local anesthetic tetracaine and normal distribution of actin cytoskeleton in yeast. Genes & genetic systems 35 16394584
2017 Aspirin disrupts the mTOR-Raptor complex and potentiates the anti-cancer activities of sorafenib via mTORC1 inhibition. Cancer letters 34 28687354
2018 Chaperonin 60 sustains osteoblast autophagy and counteracts glucocorticoid aggravation of osteoporosis by chaperoning RPTOR. Cell death & disease 32 30224697
2012 Inducible raptor and rictor knockout mouse embryonic fibroblasts. Methods in molecular biology (Clifton, N.J.) 32 22125071
2011 Raptor and Rheb negatively regulate skeletal myogenesis through suppression of insulin receptor substrate 1 (IRS1). The Journal of biological chemistry 32 21852229
2007 Discrete functions of rictor and raptor in cell growth regulation in Drosophila. Biochemical and biophysical research communications 32 17462592
2019 RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1. Cancer medicine 31 31886628
2012 Intestinal cell kinase (ICK) promotes activation of mTOR complex 1 (mTORC1) through phosphorylation of Raptor Thr-908. The Journal of biological chemistry 31 22356909
2020 Hepatic peroxisomal β-oxidation suppresses lipophagy via RPTOR acetylation and MTOR activation. Autophagy 30 32687428
2019 The MTORC1-mediated autophagy is regulated by the FBXW7-SHOC2-RPTOR axis. Autophagy 30 31010381
2018 Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells. International journal of oncology 30 29344641
2016 DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA. Oncotarget 30 27577081
2009 Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation. Molecular immunology 30 19586661
2016 Acute stimulation of glucose influx upon mitoenergetic dysfunction requires LKB1, AMPK, Sirt2 and mTOR-RAPTOR. Journal of cell science 29 27793977
2021 VHL suppresses RAPTOR and inhibits mTORC1 signaling in clear cell renal cell carcinoma. Scientific reports 28 34290272
2017 Specialized photoreceptor composition in the raptor fovea. The Journal of comparative neurology 28 28199005
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
2020 Aspirin has a better effect on PIK3CA mutant colorectal cancer cells by PI3K/Akt/Raptor pathway. Molecular medicine (Cambridge, Mass.) 27 32000660
2018 Macrophage Raptor Deficiency-Induced Lysosome Dysfunction Exacerbates Nonalcoholic Steatohepatitis. Cellular and molecular gastroenterology and hepatology 27 30539788
2013 Distribution and association of mTOR with its cofactors, raptor and rictor, in cumulus cells and oocytes during meiotic maturation in mice. Molecular reproduction and development 26 23440873
2014 Autophagy is induced by raptor degradation via the ubiquitin/proteasome system in granular corneal dystrophy type 2. Biochemical and biophysical research communications 25 25044116

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