Affinage

TBC1D4

TBC1 domain family member 4 · UniProt O60343

Length
1298 aa
Mass
146.6 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TBC1D4 (AS160) is a Rab GTPase-activating protein that serves as the central insulin- and contraction-responsive brake on regulated GLUT4 vesicle trafficking, coupling kinase signaling to membrane fusion (PMID:15971998, PMID:16213228). Its recombinant GAP domain hydrolyzes GTP on Rabs 2A, 8A, 10, and 14, an activity destroyed by mutation of the catalytic arginine, and crystallography defines an all-α-helical Rab-binding fold whose interface residues are required for catalysis and GLUT4 translocation (PMID:15971998, PMID:21454505). In the basal state TBC1D4 docks onto GLUT4 storage vesicles through its second PTB domain, which binds the cytosolic tail of IRAP and, via a distinct phospholipid-binding region, mediates vesicle versus plasma-membrane targeting; this membrane association keeps target Rabs (notably Rab8A and Rab10) GDP-bound and retains GLUT4 intracellularly, since knockdown or GAP-dead rescue releases GLUT4 to the surface (PMID:16154996, PMID:16762977, PMID:23045393, PMID:17403373, PMID:18650435). Insulin drives Akt2 to phosphorylate the critical Thr642 (mouse Thr649), recruiting 14-3-3 and disrupting the IRAP/membrane interaction, thereby relieving the Rab brake to permit GLUT4 vesicle docking and fusion; knockin of the non-phosphorylatable Thr649Ala allele impairs muscle glucose disposal in vivo (PMID:16880201, PMID:21195350, PMID:18801932, PMID:18063571). A parallel contraction/exercise pathway uses AMPK-α2, which directly phosphorylates TBC1D4 including Ser711, the site required for post-exercise insulin sensitization but dispensable for acute contraction-stimulated uptake (PMID:16804077, PMID:16804075, PMID:19923418, PMID:37074686, PMID:34753801). Phosphorylation regulates vesicle recruitment rather than intrinsic catalysis, as full-length oligomeric TBC1D4 retains GAP activity after Akt or AMPK phosphorylation while losing IRAP binding (PMID:33872597). Beyond acute trafficking, the GAP activity maintains GLUT4 protein abundance by preventing its lysosomal degradation, and combined loss of TBC1D4 and TBC1D1 abolishes insulin-stimulated glucose uptake in muscle and fat (PMID:27554475, PMID:25249576). The same phospho-regulated Rab-GAP logic governs trafficking of additional cargoes including CD36, the Na+/K+-ATPase, ENaC, and AQP2, and TBC1D4 further restrains cell proliferation through p21 (PMID:22315395, PMID:20943949, PMID:20410134, PMID:21511697, PMID:27152871).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2005 High

    Established that AS160/TBC1D4 is an enzyme with defined Rab-GAP activity and a catalytic arginine, identifying its biochemical mechanism of action.

    Evidence In vitro GAP assay with recombinant GAP domain and catalytic arginine-to-lysine mutagenesis, plus MS of GLUT4-vesicle Rabs

    PMID:15971998

    Open questions at the time
    • In vitro Rab specificity did not establish which Rabs are physiological in-cell targets
    • No structure of the catalytic domain at this stage
  2. 2005 High

    Showed that AS160 physically docks on GLUT4 vesicles via IRAP and acts as a basal-state inhibitor, explaining how a cytosolic GAP is targeted to its trafficking compartment.

    Evidence GLUT4-vesicle proteomics, reciprocal IRAP co-IP, and shRNA knockdown with GLUT4 surface measurement in adipocytes

    PMID:16154996 PMID:16213228

    Open questions at the time
    • Did not identify the downstream Rab effector relieved upon dissociation
    • Mechanism linking GAP activity to retention not yet resolved
  3. 2004 High

    Localized AS160 action to the GLUT4 exocytic limb, specifically before vesicle fusion, distinguishing it from endocytic regulation.

    Evidence Dominant-inhibitory AS160 mutant with quantitative exo/endocytosis assays in adipocytes

    PMID:15254270

    Open questions at the time
    • Did not pinpoint docking versus fusion sub-step
    • No molecular identity of the blocked Rab
  4. 2006 High

    Defined the insulin-input mechanism: Akt-dependent phosphorylation at Thr642 creates a 14-3-3 binding site that relieves inhibition, and dual kinase inputs (Akt2 for insulin, AMPK-α2 for contraction) converge on AS160.

    Evidence LC-MS/MS 14-3-3 capture, phosphosite mutagenesis, GLUT4 translocation assays, plus Akt2-KO and AMPK transgenic mouse phosphorylation studies and cell-free AMPK kinase assays

    PMID:16762977 PMID:16804075 PMID:16804077 PMID:16880201

    Open questions at the time
    • Whether 14-3-3 binding alters GAP catalysis or only localization was unresolved
    • Functional Rab targets relieved by phosphorylation not yet defined in cells
  5. 2007 High

    Identified the in-cell Rab effectors (Rab8A, Rab10, Rab14) downstream of AS160, converting in vitro substrates into a physiological pathway and placing Rab8A downstream of AS160 phosphorylation.

    Evidence Constitutively active/dominant Rab rescue and siRNA epistasis in L6 and adipocytes, with Rac/actin and VAMP2 perturbations dissecting trafficking steps

    PMID:17208202 PMID:17403373 PMID:18063571 PMID:18650435

    Open questions at the time
    • Cell-type-specific dominance of Rab8A versus Rab10 not fully reconciled
    • Docking versus fusion contributions of individual Rabs not separated
  6. 2007 High

    Mapped the multi-site phospho-code and additional regulatory domains, showing distinct kinases (RSK1, SGK1, PKB, AMPK) and a calmodulin-binding domain selectively gating contraction responses.

    Evidence MS phosphosite mapping, in vitro kinase assays with multiple kinases, and in vivo CBD-mutant electroporation with glucose uptake

    PMID:16935857 PMID:17259386 PMID:17617058 PMID:17717281

    Open questions at the time
    • Functional consequence of most individual sites beyond Thr642 unresolved
    • How calmodulin modulates GAP activity mechanistically not defined
  7. 2008 High

    Refined the targeting logic: membrane/GSV association via the PTB2 region confers the basal inhibitory effect, separating localization from catalysis.

    Evidence Subcellular fractionation and membrane-targeting/phosphomutant constructs in adipocytes

    PMID:18801932 PMID:23045393

    Open questions at the time
    • Whether dissociation per se is dispensable versus phosphorylation remained debated across constructs
    • Lipid identity driving membrane binding not fully defined
  8. 2011 High

    Provided in vivo genetic and structural proof that Thr649 phosphorylation and the GAP fold are required for muscle insulin action.

    Evidence Thr649Ala knockin mice with hyperinsulinemic-euglycemic clamp and muscle glucose transport, plus X-ray crystallography of the GAP domain with mutagenesis

    PMID:21195350 PMID:21454505

    Open questions at the time
    • Tissue divergence (muscle versus adipocyte phenotype) mechanism unexplained
    • Full-length protein architecture beyond GAP domain unknown
  9. 2016 High

    Showed a second, slower function of GAP activity: maintaining GLUT4 protein levels by preventing lysosomal degradation, and demonstrated genetic redundancy with TBC1D1.

    Evidence RabGAP-inactive R917K knockin and muscle-specific KO with lysosome-inhibition rescue, plus Tbc1d1/Tbc1d4 double-KO clamp studies

    PMID:25249576 PMID:27554475

    Open questions at the time
    • Which Rab(s) route GLUT4 to lysosomes not identified
    • Division of labor between TBC1D1 and TBC1D4 substrates incompletely resolved
  10. 2021 High

    Resolved the long-standing question of whether phosphorylation regulates catalysis versus recruitment, showing full-length oligomeric TBC1D4 retains GAP activity but loses IRAP binding upon Akt/AMPK phosphorylation.

    Evidence Baculovirus full-length protein, size-exclusion chromatography, Michaelis-Menten kinetics with isotope-labeled ATP, MS site mapping, and co-IP

    PMID:33872597

    Open questions at the time
    • Structural basis of oligomerization not determined
    • How recruitment loss translates to Rab activation in vivo not directly visualized
  11. 2023 High

    Defined the molecular basis of exercise-induced insulin sensitization, attributing it specifically to AMPK phosphorylation of Ser711.

    Evidence TBC1D4-S711A knockin mice with contraction protocols and hyperinsulinemic-euglycemic clamps, plus the earlier AS160-KO rat AAV rescue series

    PMID:19923418 PMID:34753801 PMID:37074686

    Open questions at the time
    • Downstream effector linking Ser711 to sustained sensitization unknown
    • Whether human Ser711-equivalent behaves identically not addressed
  12. 2018 Medium

    Generalized the TBC1D4 mechanism to other cargoes and contexts, showing analogous phospho-regulated Rab-GAP control of CD36, Na+/K+-ATPase, ENaC, AQP2, GLUT1, lipid droplet fusion, cell proliferation, and even pathogen-driven trafficking.

    Evidence Knockdown/overexpression, domain mapping, phosphosite mutagenesis, and trafficking/electrophysiology readouts across cardiomyocytes, kidney epithelia, adipocytes, beta-cells, cancer cells, and Chlamydia-infected cells

    PMID:18276765 PMID:20410134 PMID:20937822 PMID:20943949 PMID:21511697 PMID:22315395 PMID:25158853 PMID:27152871 PMID:31001235 PMID:31816312

    Open questions at the time
    • Most non-GLUT4 cargoes shown in single labs without in vivo genetic confirmation
    • Shared versus cargo-specific Rab effectors not systematically mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the network of upstream regulators (PP1-α, FKBP51, RIP140, RUVBL2, ClipR-59, WNK1, Rip11) integrates with the core Akt/AMPK–14-3-3 axis to set GAP activity quantitatively in different tissues remains unresolved.
  • No unified quantitative model of phospho-input integration
  • Most regulators validated in single cell systems without genetic in vivo data
  • Structural basis of full-length regulation incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0060090 molecular adaptor activity 2 GO:0008289 lipid binding 1
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2 GO:0005811 lipid droplet 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3 R-HSA-1640170 Cell Cycle 1
Partners
AKT2IRAPPRKAA2RAB10RAB14RAB8AWNK1YWHAB

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 The recombinant GAP domain of AS160/TBC1D4 has Rab GTPase-activating protein activity with specificity toward Rabs 2A, 8A, 10, and 14; a point mutation replacing the catalytic arginine with lysine abolishes this activity. In vitro GAP activity assay with recombinant GAP domain; active-site mutagenesis (R→K); mass spectrometry identification of Rabs on GLUT4 vesicles The Biochemical journal High 15971998
2005 AS160/TBC1D4 associates with GLUT4 vesicles in basal adipocytes and dissociates upon insulin stimulation; this association is mediated by the cytosolic tail of insulin-regulated aminopeptidase (IRAP). shRNA knockdown of AS160 increases plasma membrane GLUT4 in an insulin-independent manner, consistent with an inhibitory role in the basal state. Proteomic analysis of affinity-purified GLUT4 vesicles; in vitro and in vivo co-immunoprecipitation with IRAP; shRNA knockdown with GLUT4 surface measurement The Journal of biological chemistry High 16154996
2005 AS160/TBC1D4 RabGAP activity is required for basal GLUT4 retention: knockdown increases basal GLUT4 exocytosis 3-fold, and re-expression of wild-type but not a GAP-dead mutant restores normal GLUT4 behavior. shRNA knockdown; rescue with wild-type vs. GAP-domain mutant AS160; GLUT4 exocytosis rate measurement in 3T3-L1 adipocytes Cell metabolism High 16213228
2004 AS160/TBC1D4 is required specifically for insulin stimulation of GLUT4 exocytosis but not for insulin-induced inhibition of GLUT4 endocytosis; a dominant-inhibitory mutant blocks exocytosis at a step before vesicle fusion with the plasma membrane. Dominant-inhibitory AS160 mutant overexpression; quantitative GLUT4 exocytosis and endocytosis assays in adipocytes Molecular biology of the cell High 15254270
2006 14-3-3 proteins interact with AS160/TBC1D4 in an insulin- and Akt-dependent manner primarily through phospho-Thr642; the AS160(T642A) mutant lacks 14-3-3 binding and blocks insulin-stimulated GLUT4 translocation; introducing a constitutive 14-3-3 binding site into AS160(4P) restores GLUT4 translocation without disrupting IRAP interaction. LC-MS/MS identification of 14-3-3 as AS160-interacting proteins; co-immunoprecipitation; site-directed mutagenesis; GLUT4 translocation assay in adipocytes The Journal of biological chemistry High 16880201
2006 Rab8A and Rab14 (but not Rab10) act as functional targets of AS160 in L6 muscle cells: co-expression of GFP-Rab8A or GFP-Rab14 with phosphorylation-deficient AS160 (4P) rescued GLUT4 translocation inhibited by 4P-AS160; constitutively active Rab8A also rescued. Co-expression rescue assay in L6 myoblasts expressing GLUT4myc; constitutively active and wild-type Rab overexpression Biochemical and biophysical research communications Medium 17208202
2007 Rab10 is a downstream effector of AS160 in adipocytes: overexpression of GTPase-deficient Rab10 increases surface GLUT4 in basal cells; Rab10 knockdown attenuates insulin-induced GLUT4 redistribution; knocking down Rab10 in AS160-knockdown cells partially blocks the basal increase in plasma membrane GLUT4. Rab10 constitutively active mutant overexpression; siRNA knockdown; double-knockdown epistasis; GLUT4 surface assay in adipocytes Cell metabolism High 17403373
2006 AS160 phosphorylation in skeletal muscle is regulated by at least two kinase pathways: insulin-stimulated phosphorylation requires Akt2 (blocked by wortmannin and absent in Akt2-KO mice), whereas contraction-stimulated phosphorylation is only partially reduced by Akt2 loss and is fully blocked by AICAR in AMPK-α2 transgenic mice, implicating AMPK-α2 as a distinct upstream kinase. In vivo and ex vivo phosphorylation of AS160 in Akt2-KO mice, AMPK-α2-kinase-dead transgenic mice, with wortmannin treatment; immunoblot with phospho-Akt substrate antibody Diabetes High 16804077
2006 Recombinant AMPK heterotrimeric complexes (α1β1γ1 and α2β2γ1) directly phosphorylate AS160 in a cell-free assay; AICAR-stimulated AS160 phosphorylation in intact skeletal muscle requires AMPK-α2 and γ3 subunits. Cell-free phosphorylation assay with purified recombinant AMPK; AICAR treatment in AMPK-α2-KO, AMPK-α2-KD, and γ3-KO mice Diabetes High 16804075
2006 Overexpression of phosphorylation-deficient AS160 (4P mutant) significantly inhibits both insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle in vivo; this inhibition requires intact RabGAP activity, as the RabGAP-dead double mutant does not inhibit. In vivo electroporation of wild-type, 4P, R/K, and double-mutant AS160 into mouse tibialis anterior; in vivo [3H]2-deoxyglucose uptake after insulin or contraction The Journal of biological chemistry High 16935857
2007 AS160 contains a calmodulin-binding domain (CBD) that is required specifically for contraction-stimulated (but not insulin-stimulated) glucose uptake in mouse skeletal muscle; CBD mutation impairs contraction-stimulated glucose uptake, and this effect is rescued by also mutating the RabGAP domain (R/K), implying calmodulin regulates AS160 RabGAP activity during contraction. In vivo electroporation of CBD-mutant AS160; immunoprecipitation with biotinylated calmodulin; in vivo glucose uptake measurement Diabetes High 17717281
2007 Eight residues on AS160 (Ser318, Ser341, Thr568, Ser570, Ser588, Thr642, Ser666, Ser751) are differentially phosphorylated in response to IGF-1, EGF, PMA, and AICAR; 14-3-3 binding requires primarily Thr642, and is abolished by Thr642Ala/Ser341Ala double mutation; RSK1, SGK1, and PKB each display distinct phosphorylation signatures on AS160 in vitro. 14-3-3 affinity chromatography; mass spectrometry phosphosite mapping; in vitro kinase assays with RSK1, SGK1, PKB, AMPK; mutagenesis of phosphorylation sites The Biochemical journal High 17617058
2008 AS160 phosphorylation by Akt, conventional/novel PKC, and AMPK-α2 converges to regulate GLUT4 translocation; nonphosphorylatable AS160 (4P) blocks GLUT4 translocation induced by insulin, PDGF, K+ depolarization, and AICAR, but not hypertonicity or 2,4-DNP; GAP-inactive AS160 mutants have no inhibitory effect. Overexpression of 4P-AS160, RK-AS160, and 4PRK-AS160 mutants in CHO-IR and muscle cells; quantification of surface GLUT4myc with various stimuli Diabetes High 17259386
2006 AS160/TBC1D4 interacts with the amino terminus of IRAP through its second phosphotyrosine-binding (PTB) domain; this interaction is not regulated by AS160 phosphorylation; co-localization confirmed by confocal microscopy. Co-immunoprecipitation of overexpressed and endogenous proteins; confocal microscopy; domain mapping with PTB constructs Molecular endocrinology High 16762977
2008 The membrane association of TBC1D4/AS160 with GLUT4-containing membranes is required for its inhibitory action on GLUT4 translocation under basal conditions; insulin-dependent dissociation from membranes is not required for GLUT4 translocation, but phosphorylation of TBC1D4 at T642 is essential. Subcellular fractionation; overexpression of phosphorylation and membrane-targeting mutants; GLUT4 translocation assay in adipocytes Molecular endocrinology High 18801932
2009 A novel phosphorylation site, Ser711, on TBC1D4/AS160 is phosphorylated by AMPK (but not Akt1, Akt2, or PKCζ) in vitro; AICAR and contraction increase Ser711 phosphorylation in mouse skeletal muscle in an AMPK-α2-dependent manner; however, S711A mutation does not alter glucose uptake. Mass spectrometry phosphosite identification; in vitro kinase assay with purified recombinant AMPK, Akt1, Akt2, PKCζ; phosphospecific antibody; AMPK-α2 kinase-dead transgenic mice; S711A mutant glucose uptake assay American journal of physiology. Cell physiology High 19923418
2011 Knockin mutation of AS160-Thr649Ala (equivalent to human Thr642) in mice abolishes insulin-stimulated AS160 binding to 14-3-3 proteins, impairs glucose disposal and insulin sensitivity, and reduces insulin-stimulated glucose transport and cell surface GLUT4 in isolated muscles (but not adipocytes), providing genetic evidence that Thr649 phosphorylation is required for insulin action in muscle. Knockin mouse generation (Thr649Ala); hyperinsulinemic-euglycemic clamp; isolated muscle glucose transport assay; GLUT4 surface measurement; 14-3-3 co-immunoprecipitation Cell metabolism High 21195350
2011 Crystal structures of the RabGAP domains of human TBC1D4 (AS160) and TBC1D1 were solved at 3.5 Å and 2.2 Å resolution, respectively; both contain 16 α-helices and no β-sheets; alanine-scanning mutagenesis identified key residues (including Met930 in TBC1D1) required for catalytic activity and GLUT4 translocation. X-ray crystallography; alanine-scanning mutagenesis of predicted Rab-binding interface; GLUT4 translocation assay The Journal of biological chemistry High 21454505
2012 The second PTB domain of TBC1D4/AS160 contains a phospholipid-binding domain that facilitates plasma membrane targeting; a distinct non-overlapping region within this domain binds intracellular GLUT4-containing storage vesicles (GSVs). The interaction with GSVs (not plasma membrane) confers the inhibitory effect on GLUT4 translocation; constitutive targeting of AS160 to the plasma membrane increases surface GLUT4 by enhancing AS160 phosphorylation, 14-3-3 binding, and inhibiting GAP activity. Mutagenesis of phospholipid-binding domain; subcellular targeting constructs; GLUT4 translocation assay; phospholipid-binding assay; co-immunoprecipitation in adipocytes Molecular and cellular biology High 23045393
2014 Rab8a acts as a downstream effector of AS160 in a ternary complex with Fsp27 to positively regulate lipid droplet (LD) fusion in adipocytes; GDP-bound (not GTP-bound) Rab8a exhibits fusion-promoting activity; AS160 is the GAP for Rab8a; MSS4 antagonizes Fsp27-mediated LD fusion through Rab8a. Co-immunoprecipitation; shRNA knockdown of Rab8a in ob/ob mouse livers; overexpression studies; LD fusion assay in adipocytes Developmental cell High 25158853
2012 AS160 mediates insulin- and AMPK-stimulated surface translocation of CD36 in cardiomyocytes through Rab8a; AS160 knockdown redistributes CD36 to the surface and abrogates stimulated recruitment; phosphorylation-deficient AS160 (4P) suppresses stimulated CD36 membrane recruitment; Rab8a overexpression and knockdown specifically modulates insulin/AICAR-induced CD36 translocation. AS160 and Rab8a knockdown and overexpression in cardiomyocytes; CD36 surface measurement; GLUT4 and CD36 translocation assays Journal of lipid research High 22315395
2014 Combined deletion of TBC1D1 and TBC1D4 in mice (D1/4KO) almost completely abolishes insulin-stimulated glucose uptake in muscle and adipose cells, with substantially reduced GLUT4 protein levels; single knockouts show only partial impairment, indicating non-redundant but overlapping roles. Double knockout (Tbc1d1/Tbc1d4 KO) mouse; euglycemic-hyperinsulinemic clamp; isolated muscle and adipocyte glucose uptake; GLUT4 protein quantification; cell surface GLUT4 labeling Diabetes High 25249576
2016 The RabGAP activity of AS160 is specifically required to maintain GLUT4 protein levels in a cell/tissue-autonomous manner; the RabGAP-inactive AS160(R917K) knockin mouse phenocopies the AS160-KO, and inhibition of lysosomal function restores GLUT4 protein levels, indicating that loss of AS160 RabGAP activity promotes lysosomal degradation of GLUT4. Muscle-specific AS160 KO; RabGAP-inactive AS160(R917K) knockin mouse; lysosome inhibition rescue; GLUT4 protein measurement Diabetes High 27554475
2021 Full-length TBC1D4 forms oligomers of ~600 kDa and has markedly higher specific GAP activity toward Rab10 compared with the truncated GAP domain alone; AKT phosphorylates TBC1D4 preferentially at Ser324 and Thr649, while AMPK preferentially phosphorylates Ser348, Ser577, Ser595, Ser711, and Ser764; phosphorylation by AKT or AMPK does not alter intrinsic RabGAP activity but disrupts interaction with IRAP, suggesting phosphorylation regulates TBC1D4 vesicle recruitment rather than catalytic activity. Baculovirus-expressed recombinant full-length TBC1D4; size-exclusion chromatography; co-immunoprecipitation; high-resolution mass spectrometry; Michaelis-Menten kinetics with stable isotope-labeled γ-[18O4]-ATP; in vitro phosphorylation assays with purified AKT and AMPK The Journal of biological chemistry High 33872597
2007 AS160 phosphorylation is required for the docking step of GLUT4 storage vesicles (GSVs) at the plasma membrane; quantitative dual-color fluorescence assay revealed that a dominant-negative AS160 mutant proportionally inhibits both docking and fusion of GSVs, indicating AS160 acts at or before docking but not in the regulation of GSV fusion after docking. Novel dual-color fluorescent GLUT4 probe; single-vesicle fusion assay; dominant-negative AS160 mutant overexpression in 3T3-L1 adipocytes The Journal of biological chemistry Medium 18063571
2008 GLUT4 vesicle recruitment to the cell periphery requires Rac/actin dynamics, while AS160 phosphorylation (acting through Rab8A) is essential for vesicle docking/fusion; selective Rab8A knockdown magnifies the effect of non-phosphorylatable AS160 (4P) on blocking GLUT4 insertion, placing Rab8A downstream of AS160. Dominant-negative Rac; latrunculin B actin disruption; tetanus toxin VAMP2 cleavage; non-phosphorylatable AS160-4P; selective Rab8A siRNA knockdown; GLUT4myc insertion assay in L6 myoblasts The Journal of biological chemistry High 18650435
2010 AS160 directly interacts with the NP domain of the Na+,K+-ATPase α-subunit; AS160 coexpression causes intracellular retention of the sodium pump; AMPK-dependent phosphorylation of AS160 regulates Na+,K+-ATPase cell surface expression, as AMPK inhibition-induced endocytosis of the pump is prevented by AS160 shRNA knockdown. Co-immunoprecipitation; co-expression in COS cells; domain mapping; shRNA knockdown; pharmacological AMPK inhibition (Compound C); Na+,K+-ATPase surface expression assay Molecular biology of the cell Medium 20943949
2010 Aldosterone increases AS160 expression and induces AS160 phosphorylation predominantly at SGK1 sites (Thr568 and Ser751), promoting AS160 interaction with 14-3-3β and ε; AS160 stabilizes ENaC in intracellular compartments under basal conditions, and aldosterone/SGK1-dependent AS160 phosphorylation permits ENaC forward trafficking to the apical membrane. AS160 overexpression and knockdown in cortical collecting duct epithelial cells; 14-3-3 co-immunoprecipitation; mutagenesis of SGK1 phospho-sites; amiloride-sensitive Na+ current measurement; apical membrane biotinylation Molecular biology of the cell High 20410134
2011 AS160 knockdown in 3T3-L1 adipocytes releases GLUT4 from intracellular retention into the actively cycling pool without changing the exocytosis rate constant (kex) or endocytosis rate constant (ken); Akt regulates kex through an AS160-independent mechanism, indicating AS160 controls GLUT4 vesicle tethering/docking/fusion through Rab GTP-hydrolysis, while a separate Akt substrate regulates the final fusion step. Kinetic modeling of GLUT4 trafficking; shRNA knockdown; PI3K/Akt inhibitor treatments; mathematical modeling The Journal of biological chemistry Medium 21613213
2009 Cytoplasmic RIP140 (exported from the nucleus after PKCε phosphorylation and arginine methylation) interacts directly with AS160 to impede AS160 phosphorylation by Akt, thereby reducing GLUT4 trafficking and glucose uptake in adipocytes; this pathway is activated in epididymal adipocytes of diet-induced obese mice. Co-immunoprecipitation; AS160 phosphorylation assay; GLUT4 translocation assay; in vivo diet-induced obesity model Cell metabolism Medium 19945409
2007 Rip11 forms a protein complex with AS160 in a Rab11-independent manner in adipocytes; insulin induces dissociation of AS160 from Rip11; Rip11 knockdown inhibits insulin-stimulated glucose uptake, and Rip11 overexpression blocks insertion of translocated GLUT4 vesicles into the plasma membrane. Co-immunoprecipitation; siRNA knockdown; Rip11 overexpression; GLUT4 vesicle insertion assay; 2-deoxyglucose uptake in 3T3-L1 adipocytes Journal of cell science Medium 18003705
2009 RUVBL2 is a novel AS160-binding protein identified by tandem affinity purification/mass spectrometry; depletion of RUVBL2 in 3T3-L1 adipocytes inhibits insulin-stimulated GLUT4 translocation and glucose uptake by reducing insulin-stimulated AS160 phosphorylation; re-introduction of human RUVBL2 reverses the inhibitory effect. Mammalian TAP combined with mass spectrometry; siRNA knockdown; rescue re-expression; GLUT4 translocation assay Cell research Medium 19532121
2012 ClipR-59 interacts directly with AS160 through its ankyrin repeats; this interaction is required for ClipR-59 to promote AS160 phosphorylation and GLUT4 membrane translocation; ClipR-59 functions as a scaffold facilitating Akt-mediated AS160 phosphorylation. Co-immunoprecipitation; ankyrin-repeat deletion mutant (ΔANK); GLUT4 translocation assay; glucose transport measurement in 3T3-L1 adipocytes The Journal of biological chemistry Medium 22689584
2011 AS160 knockdown in mouse cortical collecting duct cells (mpkCCDc14) increases AQP2 density at the plasma membrane in the absence of dDAVP stimulation; phosphorylation of AS160 is dependent on PI3K/Akt pathway (Akt1 knockdown reduces phospho-AS160); these findings suggest AS160 RabGAP activity restrains AQP2 trafficking to the plasma membrane. siRNA knockdown of AS160 and Akt1; immunocytochemistry; cell surface biotinylation; dDAVP stimulation in M-1 and mpkCCDc14 cells American journal of physiology. Renal physiology Medium 21511697
2010 WNK1 phosphorylates TBC1D4 in vitro, forms a protein complex with TBC1D4 in HEK293 cells, increases TBC1D4 binding to 14-3-3 proteins, reduces TBC1D4 interaction with Rab8A, and regulates cell surface expression of GLUT1; these effects require WNK1 catalytic activity. Co-immunoprecipitation; in vitro phosphorylation by WNK1; kinase-dead mutant; GLUT1 surface expression assay The Journal of biological chemistry Medium 20937822
2019 WNK1 phosphorylates TBC1D4 at Ser704 (identified by mass spectrometry); WNK1 knockdown decreases plasma membrane GLUT1 and glucose uptake; phosphomimetic and unphosphorylatable Ser704 mutants of TBC1D4 each affect cell surface GLUT1 abundance. RNA interference of WNK1; mass spectrometry phosphosite identification; phosphomimetic and alanine substitution mutants; GLUT1 surface quantification Archives of biochemistry and biophysics Medium 31816312
2017 FKBP51 forms a novel physical association with AS160; FKBP51 antagonism (SAFit2) or genetic deletion increases AS160 phosphorylation and enhances GLUT4 surface expression and glucose uptake in skeletal myotubes, placing FKBP51 as a negative regulator upstream of the AKT2-AS160 axis. Co-immunoprecipitation; phosphorylation immunoblot; GLUT4 surface assay; FKBP51 KO mice; SAFit2 pharmacological treatment Nature communications Medium 29170369
2016 Rab28 is a substrate for the GAP domains of both TBC1D4 and TBC1D1 in vitro; Rab28 GTP-binding state is acutely regulated by insulin in vivo; Rab28 siRNA knockdown decreases basal glucose uptake in skeletal muscle, and constitutively active Rab28 increases basal GLUT4 surface levels in adipocytes. In vitro GAP activity assay; GTP-binding measurement; siRNA knockdown in isolated muscle; constitutively active Rab28-Q72L overexpression FEBS letters Medium 27929607
2016 AS160 knockdown causes blunted cell proliferation and G1 phase arrest in multiple cell lines in a glucose-independent manner; this is mediated by upregulation of the CDK inhibitor p21; AS160 overexpression downregulates p21 and rescues arrested cell cycle; p21 knockdown rescues the proliferation defect caused by AS160 depletion. shRNA knockdown in fibroblasts and cancer cells; cell cycle analysis; p21 immunoblot; AS160 overexpression rescue; p21 siRNA double knockdown Cell cycle Medium 27152871
2018 AS160 (TBC1D4) acts as the Rab14 GAP within Chlamydia trachomatis-infected cells; bacterial infection induces Akt phosphorylation and phosphorylation/inactivation of AS160 at the inclusion membrane, thereby maintaining Rab14 in the GTP-bound state to facilitate sphingolipid delivery to chlamydial inclusions; Akt inhibition prevents AS160 phosphorylation, reduces Rab14 at inclusions, and impairs bacterial replication. Pharmacological Akt inhibition; AS160 siRNA knockdown; immunofluorescence; electron microscopy; sphingolipid trafficking assay Frontiers in microbiology Medium 31001235
2016 AS160 phosphorylation on Ser588 and Thr642 is regulated by PP1-α: PP1-α co-immunoprecipitates with AS160 (not PP1-β, PP1-γ1, or PP2A); recombinant PP1 inhibitor-2 delays AS160 dephosphorylation; PP1-α siRNA knockdown increases AS160 phosphorylation on both sites without altering Akt phosphorylation. Co-immunoprecipitation of PP1 isoforms with AS160; pharmacological phosphatase inhibitor treatment; recombinant inhibitor-2 protein; PP1-α/β/γ1 siRNA knockdown; phosphospecific immunoblot Diabetes High 27246912
2023 TBC1D4-Ser711 phosphorylation by AMPK mediates the insulin-sensitizing effect of exercise on skeletal muscle glucose uptake: TBC1D4-S711A knockin mice show normal contraction-stimulated glucose uptake but lack the post-exercise/contraction enhancement of insulin sensitivity observed in wild-type mice; enhanced TBC1D4-S711 phosphorylation occurs concomitantly with improved insulin sensitivity after exercise. TBC1D4-S711A knockin mouse; in vitro contraction; hyperinsulinemic-euglycemic clamp; glucose uptake measurement; AMPK activity assay; phosphospecific immunoblot Diabetes High 37074686
2018 In cells co-expressing both TBC1D4 and TBC1D1, Tbc1d1 functionally dominates AS160/TBC1D4, and GLUT4 release relies on Tbc1d1-evoking proximal stimuli (AICAR, Ca2+); AS160 modulates sensitivity to stimuli in Tbc1d1-mediated GLUT4 release; cooperative actions require the PTB1 and calmodulin-binding domains of Tbc1d1 and phosphorylation sites on both AS160 (Thr642) and Tbc1d1 (Ser237, Thr596). GLUT4 nanometry; cell-based reconstitution; varying expression ratios; mutational analyses of multiple domains and phosphorylation sites The Journal of biological chemistry Medium 30482843
2022 AS160 expression is essential for post-exercise enhancement of insulin-stimulated glucose uptake (ISGU) in skeletal muscle: AS160-KO rats lack post-exercise improvement in ISGU; AAV-mediated rescue of AS160 in AS160-KO muscle restores this enhancement; AAV-delivered GLUT4 alone does not rescue; AS160 mutated at Ser588/Thr642/Ser704 only partially restores the post-exercise effect. AS160-KO rat model; AAV-mediated gene delivery of wild-type or phosphomutant AS160 and GLUT4; isolated muscle glucose uptake assay post-exercise Diabetes High 34753801
2008 AS160 is expressed in pancreatic beta-cells and phosphorylated after glucose stimulation via insulin receptor/IRS-2/PI3K/Akt, independently of cytosolic Ca2+; AS160 knockdown in MIN6B1 beta-cells increases basal insulin secretion, abolishes glucose-stimulated insulin release, increases apoptosis, and eliminates glucose-induced proliferation. shRNA knockdown and siRNA in MIN6B1 and primary mouse islet cells; AS160 phosphorylation immunoblot; insulin secretion assay; apoptosis measurement Diabetes Medium 18276765

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic. American journal of physiology. Endocrinology and metabolism 363 18477703
2005 AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain. The Biochemical journal 347 15971998
2005 Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking. The Journal of biological chemistry 331 16154996
2014 A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. Nature 319 25043022
2007 Rab10, a target of the AS160 Rab GAP, is required for insulin-stimulated translocation of GLUT4 to the adipocyte plasma membrane. Cell metabolism 299 17403373
2006 Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle. Diabetes 266 16804077
2005 Full intracellular retention of GLUT4 requires AS160 Rab GTPase activating protein. Cell metabolism 262 16213228
2005 Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects. Diabetes 234 15919790
2006 AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle. The Journal of biological chemistry 229 16935857
2006 AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits. Diabetes 220 16804075
2005 Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity. Diabetes 215 15616009
2007 The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic. Diabetes 192 17259386
2004 Insulin stimulation of GLUT4 exocytosis, but not its inhibition of endocytosis, is dependent on RabGAP AS160. Molecular biology of the cell 187 15254270
2006 A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160. The Journal of biological chemistry 178 16880201
2008 Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators. The Biochemical journal 169 17995453
2007 Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS160. Diabetes 154 17513702
2007 Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR. The Biochemical journal 153 17617058
2011 Mice with AS160/TBC1D4-Thr649Ala knockin mutation are glucose intolerant with reduced insulin sensitivity and altered GLUT4 trafficking. Cell metabolism 145 21195350
2014 Roles of TBC1D1 and TBC1D4 in insulin- and exercise-stimulated glucose transport of skeletal muscle. Diabetologia 125 25280670
2006 Rabs 8A and 14 are targets of the insulin-regulated Rab-GAP AS160 regulating GLUT4 traffic in muscle cells. Biochemical and biophysical research communications 125 17208202
2006 AS160 phosphorylation is associated with activation of alpha2beta2gamma1- but not alpha2beta2gamma3-AMPK trimeric complex in skeletal muscle during exercise in humans. American journal of physiology. Endocrinology and metabolism 112 17077344
2014 Rab8a-AS160-MSS4 regulatory circuit controls lipid droplet fusion and growth. Developmental cell 106 25158853
2010 Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training. Diabetologia 104 20938636
2009 Potential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle. Diabetologia 104 19252894
2009 Increased AS160 phosphorylation, but not TBC1D1 phosphorylation, with increased postexercise insulin sensitivity in rat skeletal muscle. American journal of physiology. Endocrinology and metabolism 102 19435856
2006 Exercise-induced phosphorylation of the novel Akt substrates AS160 and filamin A in human skeletal muscle. Diabetes 102 16731842
2012 Insulin and AMPK regulate FA translocase/CD36 plasma membrane recruitment in cardiomyocytes via Rab GAP AS160 and Rab8a Rab GTPase. Journal of lipid research 100 22315395
2012 Electrical stimuli release ATP to increase GLUT4 translocation and glucose uptake via PI3Kγ-Akt-AS160 in skeletal muscle cells. Diabetes 100 23274898
2017 Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function. Nature communications 97 29170369
2012 Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in primary skeletal muscles and adipocytes and impairs glucose homeostasis. American journal of physiology. Endocrinology and metabolism 95 23011063
2008 GLUT4 vesicle recruitment and fusion are differentially regulated by Rac, AS160, and Rab8A in muscle cells. The Journal of biological chemistry 95 18650435
2006 Prior exercise increases phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle. American journal of physiology. Endocrinology and metabolism 94 17179389
2009 A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemia. Proceedings of the National Academy of Sciences of the United States of America 93 19470471
2009 Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle. American journal of physiology. Cell physiology 88 19923418
2006 Interaction of the Akt substrate, AS160, with the glucose transporter 4 vesicle marker protein, insulin-regulated aminopeptidase. Molecular endocrinology (Baltimore, Md.) 80 16762977
2014 “Deletion of both Rab-GTPase–activating proteins TBC1D1 and TBC1D4 in mice eliminates insulin- and AICAR-stimulated glucose transport [corrected]. Diabetes 77 25249576
2013 AS160 deficiency causes whole-body insulin resistance via composite effects in multiple tissues. The Biochemical journal 74 23078342
2014 Postexercise improvement in insulin-stimulated glucose uptake occurs concomitant with greater AS160 phosphorylation in muscle from normal and insulin-resistant rats. Diabetes 73 24608437
2007 Direct quantification of fusion rate reveals a distal role for AS160 in insulin-stimulated fusion of GLUT4 storage vesicles. The Journal of biological chemistry 72 18063571
2009 Lipid and insulin infusion-induced skeletal muscle insulin resistance is likely due to metabolic feedback and not changes in IRS-1, Akt, or AS160 phosphorylation. American journal of physiology. Endocrinology and metabolism 70 19366875
2012 The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes. Molecular and cellular biology 59 23045393
2008 Regulation of glucose transporter 4 translocation by the Rab guanosine triphosphatase-activating protein AS160/TBC1D4: role of phosphorylation and membrane association. Molecular endocrinology (Baltimore, Md.) 59 18801932
2009 Inhibition of contraction-stimulated AMP-activated protein kinase inhibits contraction-stimulated increases in PAS-TBC1D1 and glucose transport without altering PAS-AS160 in rat skeletal muscle. Diabetes 57 19208911
2017 Baicalin against obesity and insulin resistance through activation of AKT/AS160/GLUT4 pathway. Molecular and cellular endocrinology 56 28359800
2011 Clustering of GLUT4, TUG, and RUVBL2 protein levels correlate with myosin heavy chain isoform pattern in skeletal muscles, but AS160 and TBC1D1 levels do not. Journal of applied physiology (Bethesda, Md. : 1985) 52 21799128
2009 A negative regulatory pathway of GLUT4 trafficking in adipocyte: new function of RIP140 in the cytoplasm via AS160. Cell metabolism 48 19945409
2008 Rab GTPase-activating protein AS160 is a major downstream effector of protein kinase B/Akt signaling in pancreatic beta-cells. Diabetes 48 18276765
2007 Calmodulin-binding domain of AS160 regulates contraction- but not insulin-stimulated glucose uptake in skeletal muscle. Diabetes 45 17717281
2021 AKT ISOFORMS-AS160-GLUT4: The defining axis of insulin resistance. Reviews in endocrine & metabolic disorders 44 33928491
2016 Toward Precision Medicine: TBC1D4 Disruption Is Common Among the Inuit and Leads to Underdiagnosis of Type 2 Diabetes. Diabetes care 44 27561922
2007 Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation. American journal of physiology. Endocrinology and metabolism 44 17785505
2015 Rab GAPs AS160 and Tbc1d1 play nonredundant roles in the regulation of glucose and energy homeostasis in mice. American journal of physiology. Endocrinology and metabolism 42 26625902
2012 Sustained postexercise increases in AS160 Thr642 and Ser588 phosphorylation in skeletal muscle without sustained increases in kinase phosphorylation. Journal of applied physiology (Bethesda, Md. : 1985) 42 22936728
2011 Loss of AS160 Akt substrate causes Glut4 protein to accumulate in compartments that are primed for fusion in basal adipocytes. The Journal of biological chemistry 42 21613213
2010 AS160 modulates aldosterone-stimulated epithelial sodium channel forward trafficking. Molecular biology of the cell 41 20410134
2007 The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding capacity in human skeletal muscle. American journal of physiology. Endocrinology and metabolism 40 18042670
2008 Identification of a novel AS160 splice variant that regulates GLUT4 translocation and glucose-uptake in rat muscle cells. Cellular signalling 38 18771725
2016 The Inactivation of RabGAP Function of AS160 Promotes Lysosomal Degradation of GLUT4 and Causes Postprandial Hyperglycemia and Hyperinsulinemia. Diabetes 36 27554475
2007 Rip11 is a Rab11- and AS160-RabGAP-binding protein required for insulin-stimulated glucose uptake in adipocytes. Journal of cell science 36 18003705
2011 Emerging role of Akt substrate protein AS160 in the regulation of AQP2 translocation. American journal of physiology. Renal physiology 35 21511697
2010 AS160 associates with the Na+,K+-ATPase and mediates the adenosine monophosphate-stimulated protein kinase-dependent regulation of sodium pump surface expression. Molecular biology of the cell 35 20943949
2013 Insulin stimulation regulates AS160 and TBC1D1 phosphorylation sites in human skeletal muscle. Nutrition & diabetes 34 23752133
2011 Naturally occurring compensated insulin resistance selectively alters glucose transporters in visceral and subcutaneous adipose tissues without change in AS160 activation. Biochimica et biophysica acta 34 21352908
2014 Sustained AS160 and TBC1D1 phosphorylations in human skeletal muscle 30 min after a single bout of exercise. Journal of applied physiology (Bethesda, Md. : 1985) 33 24876356
2015 [6]-Gingerol Affects Glucose Metabolism by Dual Regulation via the AMPKα2-Mediated AS160-Rab5 Pathway and AMPK-Mediated Insulin Sensitizing Effects. Journal of cellular biochemistry 31 25694332
2014 Insulin-sensitizing effect of LXR agonist T0901317 in high-fat fed rats is associated with restored muscle GLUT4 expression and insulin-stimulated AS160 phosphorylation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 31 24732673
2012 Thr649Ala-AS160 knock-in mutation does not impair contraction/AICAR-induced glucose transport in mouse muscle. American journal of physiology. Endocrinology and metabolism 31 22318952
2007 Resistance exercise and insulin regulate AS160 and interaction with 14-3-3 in human skeletal muscle. Diabetes 31 17369524
2012 Astragalus polysaccharide stimulates glucose uptake in L6 myotubes through AMPK activation and AS160/TBC1D4 phosphorylation. Acta pharmacologica Sinica 29 23103623
2010 Protein kinase WNK1 promotes cell surface expression of glucose transporter GLUT1 by regulating a Tre-2/USP6-BUB2-Cdc16 domain family member 4 (TBC1D4)-Rab8A complex. The Journal of biological chemistry 29 20937822
2008 Contraction-stimulated glucose transport in rat skeletal muscle is sustained despite reversal of increased PAS-phosphorylation of AS160 and TBC1D1. Journal of applied physiology (Bethesda, Md. : 1985) 27 18818383
2018 Cooperative actions of Tbc1d1 and AS160/Tbc1d4 in GLUT4-trafficking activities. The Journal of biological chemistry 26 30482843
2020 Protective role of Astragaloside IV in chronic glomerulonephritis by activating autophagy through PI3K/AKT/AS160 pathway. Phytotherapy research : PTR 25 32726508
2022 Berberine regulates mesangial cell proliferation and cell cycle to attenuate diabetic nephropathy through the PI3K/Akt/AS160/GLUT1 signalling pathway. Journal of cellular and molecular medicine 24 35001506
2021 AKT/AMPK-mediated phosphorylation of TBC1D4 disrupts the interaction with insulin-regulated aminopeptidase. The Journal of biological chemistry 24 33872597
2014 Augmented β-Cell Function and Mass in Glucocorticoid-Treated Rodents Are Associated with Increased Islet Ir-β /AKT/mTOR and Decreased AMPK/ACC and AS160 Signaling. International journal of endocrinology 24 25313308
2011 Fatty acid-binding protein 3 stimulates glucose uptake by facilitating AS160 phosphorylation in mouse muscle cells. Genes to cells : devoted to molecular & cellular mechanisms 24 21501347
2011 Crystal structures of human TBC1D1 and TBC1D4 (AS160) RabGTPase-activating protein (RabGAP) domains reveal critical elements for GLUT4 translocation. The Journal of biological chemistry 23 21454505
2010 Disruption of AMPKalpha1 signaling prevents AICAR-induced inhibition of AS160/TBC1D4 phosphorylation and glucose uptake in primary rat adipocytes. Molecular endocrinology (Baltimore, Md.) 23 20501641
2012 Leptin reduces the expression and increases the phosphorylation of the negative regulators of GLUT4 traffic TBC1D1 and TBC1D4 in muscle of ob/ob mice. PloS one 22 22253718
2018 Postexercise improvement in glucose uptake occurs concomitant with greater γ3-AMPK activation and AS160 phosphorylation in rat skeletal muscle. American journal of physiology. Endocrinology and metabolism 21 30130149
2009 RUVBL2, a novel AS160-binding protein, regulates insulin-stimulated GLUT4 translocation. Cell research 21 19532121
2017 Challenging of AS160/TBC1D4 Alters Intracellular Lipid milieu in L6 Myotubes Incubated With Palmitate. Journal of cellular physiology 20 27714805
2013 Expression and phosphorylation of the AS160_v2 splice variant supports GLUT4 activation and the Warburg effect in multiple myeloma. Cancer & metabolism 20 24280290
2012 The association of ClipR-59 protein with AS160 modulates AS160 protein phosphorylation and adipocyte Glut4 protein membrane translocation. The Journal of biological chemistry 20 22689584
2020 Sex and fiber type independently influence AMPK, TBC1D1, and TBC1D4 at rest and during recovery from high-intensity exercise in humans. Journal of applied physiology (Bethesda, Md. : 1985) 19 31895596
2020 Resistance exercise-induced increase in muscle 5α-dihydrotestosterone contributes to the activation of muscle Akt/mTOR/p70S6K- and Akt/AS160/GLUT4-signaling pathways in type 2 diabetic rats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 32627878
2020 LNK deficiency decreases obesity-induced insulin resistance by regulating GLUT4 through the PI3K-Akt-AS160 pathway in adipose tissue. Aging 18 32911464
2019 Akt/AS160 Signaling Pathway Inhibition Impairs Infection by Decreasing Rab14-Controlled Sphingolipids Delivery to Chlamydial Inclusions. Frontiers in microbiology 18 31001235
2016 AS160 controls eukaryotic cell cycle and proliferation by regulating the CDK inhibitor p21. Cell cycle (Georgetown, Tex.) 18 27152871
2016 Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking. FEBS letters 18 27929607
2022 Exercise-Induced Improvement in Insulin-Stimulated Glucose Uptake by Rat Skeletal Muscle Is Absent in Male AS160-Knockout Rats, Partially Restored by Muscle Expression of Phosphomutated AS160, and Fully Restored by Muscle Expression of Wild-Type AS160. Diabetes 17 34753801
2016 Protein Phosphatase 1-α Regulates AS160 Ser588 and Thr642 Dephosphorylation in Skeletal Muscle. Diabetes 17 27246912
2008 Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes. Molecular and cellular endocrinology 17 19013499
2004 Upregulation of the transcript level of GTPase activating protein KIAA0603 in T cells from patients with atopic dermatitis. FEBS letters 17 15304337
2023 TBC1D4-S711 Controls Skeletal Muscle Insulin Sensitization After Exercise and Contraction. Diabetes 16 37074686
2019 WNK1 phosphorylation sites in TBC1D1 and TBC1D4 modulate cell surface expression of GLUT1. Archives of biochemistry and biophysics 16 31816312
2018 AMPK/AS160 mediates tiliroside derivatives-stimulated GLUT4 translocation in muscle cells. Drug design, development and therapy 16 29910604
2018 Estrogen replacement enhances insulin-induced AS160 activation and improves insulin sensitivity in ovariectomized rats. American journal of physiology. Endocrinology and metabolism 16 30179516
2010 Membrane Trafficking of Collecting Duct Water Channel Protein AQP2 Regulated by Akt/AS160. Electrolyte & blood pressure : E & BP 16 21468198

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