Affinage

ARF6

ADP-ribosylation factor 6 · UniProt P62330

Length
175 aa
Mass
20.1 kDa
Annotated
2026-06-09
100 papers in source corpus 59 papers cited in narrative 59 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

ARF6 is a small GTPase of the endosomal/plasma membrane system whose GTP/GDP cycle governs clathrin-independent endocytosis, cargo recycling, actin remodeling, and regulated membrane budding, distinct from Golgi-associated ARF function (PMID:7896867). A central output of activated ARF6 is the local generation of phosphoinositides: ARF6-GTP recruits and activates PIP5K to produce PI(4,5)P2 at the plasma membrane and on tubular endosomes, and PI(4,5)P2 turnover driven by the GTPase cycle is required for cargo recycling, with constitutively active ARF6 trapping integrins and other surface proteins in PI(4,5)P2-positive, actin-coated vacuoles (PMID:11535619); ARF6 inactivation and acquisition of PI3P in turn permit fusion of non-clathrin endosomes with the EEA1 pathway (PMID:12589044), and loss of ARF6 perturbs endosomal PI4P to disrupt retromer-mediated retrograde transport and cholesterol distribution (PMID:27336679). ARF6 also activates phospholipase D2 in cholesterol-dependent microdomains (PMID:15759270) and recruits the exocyst complex via PIP5K1C-generated PI(4,5)P2 to tether vesicles at the plasma membrane (PMID:35609603). Through these activities ARF6 controls receptor and integrin endocytosis/recycling—including β1-integrin handled via the GEF BRAG2/GEP100 (PMID:16461286) and recycling coordinated by ARF6-GTP binding of clathrin and JIP3/JIP4 motor scaffolds on endocytic vesicles for microtubule-dependent transferrin receptor recycling (PMID:21439824). ARF6 drives cancer cell invasion by directing MT1-MMP endosome exocytosis through JIP3/JIP4–dynein/kinesin coordination (PMID:26504170) and by promoting protease-loaded microvesicle shedding via a PLD–ERK–MLCK cascade (PMID:19896381), and its release of pre-miRNA-loaded tumor microvesicles requires a GRP1/Exportin-5 shuttle (PMID:31235936). Its cycle is set by ARF6-specific GAPs including ACAP1/2 and ACAP4 (PMID:11062263, PMID:16737952) and a diverse repertoire of GEFs (ARNO, GEP100, EFA6, GRP1, PSD4) acting downstream of receptors such as EGFR, VEGFR2, Met, DDR1, GPCRs, and Gαq (PMID:19416474, PMID:29058688, PMID:35140331), and is further tuned by Fbx8-mediated ubiquitination that inactivates ARF6 (PMID:18094045) and by reciprocal antagonism with Rab35 (PMID:22226746, PMID:23264734). Physiologically, endothelial ARF6 supports HGF-stimulated β1-integrin recycling and tumor neoangiogenesis (PMID:26239146), ARF6 controls platelet integrin trafficking and clot retraction (PMID:26738539), maintains endothelial barrier integrity downstream of IL-1β/MYD88/ARNO (PMID:23143332), and is required for cytokinesis (PMID:16181626, PMID:22226746), dendritic spine formation (PMID:16672654), and commissural axon midline crossing via Robo1 recycling (PMID:30674481).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 High

    Established that ARF6 acts in the endosomal/plasma membrane system rather than the Golgi, defining its compartment and showing that its GTPase state dictates membrane morphology.

    Evidence Immuno-EM and immunofluorescence of epitope-tagged wild-type and GTPase-mutant ARF6

    PMID:7896867

    Open questions at the time
    • Did not identify effectors linking GTP state to membrane remodeling
    • Cargo-level consequences not yet defined
  2. 2001 High

    Identified PI(4,5)P2 generation via PIP5K as the central lipid output of the ARF6 cycle controlling recycling, explaining how the GTPase remodels membranes.

    Evidence GFP-PH PI(4,5)P2 reporter with ARF6 mutants and EFA6 in cultured cells

    PMID:11535619

    Open questions at the time
    • Direct biochemical PIP5K activation kinetics not resolved here
    • How PI(4,5)P2 turnover is coupled to specific recycling steps unclear
  3. 2000 High

    Defined the GAP arm of the cycle by showing ACAP1/2 are ARF6-specific, PI-dependent GAPs acting peripherally, the first specific ARF6 inactivators.

    Evidence In vitro GAP assays with substrate specificity plus cell-based protrusion readout

    PMID:11062263

    Open questions at the time
    • Spatial recruitment cues for ACAPs in vivo not fully defined
  4. 2003 Medium

    Showed ARF6 inactivation and PI3P acquisition are required for non-clathrin endosomes to converge with the canonical EEA1 early-endosome pathway, positioning the cycle within endosome maturation.

    Evidence ARF6 mutants plus PI3-kinase inhibitors with defined cargo readouts

    PMID:12589044

    Open questions at the time
    • GAP responsible for inactivation step not identified
    • Single lab
  5. 2006 High

    Resolved spatiotemporal control of ARF6 in living cells, showing activation restricted to leading edges and switching to ARF1 downstream of a PI3K signal during phagocytosis.

    Evidence FRET stoichiometric microscopy of ARF chimeras with PI3K inhibition

    PMID:16669702

    Open questions at the time
    • GEF/GAP identities producing the spatial gradient not pinned down
  6. 2006 High

    Connected receptor trafficking machinery to ARF6 by identifying ARNO-V-ATPase coupling as an acidification-sensitive control point for endosomal progression.

    Evidence Reciprocal Co-IP, bafilomycin, dominant-negatives, endocytosis assays

    PMID:16415858

    Open questions at the time
    • How acidification state is transduced to GEF activity mechanistically unclear
  7. 2006 High

    Demonstrated ARF6 controls β1-integrin endocytosis and recycling via the GEF BRAG2/GEP100, linking the cycle to adhesion dynamics.

    Evidence siRNA of GEF and GTPase with reciprocal surface/internal integrin phenotypes

    PMID:16461286

    Open questions at the time
    • Structural basis of BRAG2 selectivity for ARF6 not addressed
  8. 2009 High

    Defined a linear ARF6-GTP→PLD→ERK→MLCK→MLC cascade driving protease-loaded microvesicle shedding, mechanistically tying ARF6 to tumor microvesicle biogenesis.

    Evidence ARF6 mutants with PLD, ERK, MLCK inhibition and vesicle quantification

    PMID:19896381

    Open questions at the time
    • Cargo selection into microvesicles not fully resolved
  9. 2011 High

    Separated ARF6 activation at clathrin-coated pits from its effector role, showing ARF6-JIP recruitment drives microtubule-dependent fast recycling rather than endocytosis itself.

    Evidence TIRF microscopy of GFP-ARF6 with AP-2 mutants and recycling assays

    PMID:21439824

    Open questions at the time
    • How AP-2 selects ARF6-GTP at CCPs mechanistically undefined
  10. 2011 High

    Placed ARF6 in reciprocal antagonism with Rab35 by identifying EPI64B as an ARF6 effector that is a Rab35-GAP, linking the two GTPases in recycling and cytokinesis.

    Evidence Constitutively active ARF6, effector identification, Rab35-GTP and cytokinesis readouts

    PMID:22226746

    Open questions at the time
    • Reciprocal Rab35-driven ARF6 suppression mechanism addressed separately
  11. 2012 High

    Extended ARF6 to vascular physiology by showing IL-1β acts through a MYD88-ARNO-ARF6 axis to disrupt endothelial junctions, validated pharmacologically in vivo.

    Evidence Direct MYD88-ARNO binding, SecinH3 inhibition, permeability and in vivo inflammation models

    PMID:23143332

    Open questions at the time
    • Junctional cargo internalized by ARF6 not enumerated here
  12. 2014 High

    Defined ARF6/PLD2 control of intraluminal vesicle budding into MVBs for syntenin exosome biogenesis, distinct from general ESCRT-dependent budding.

    Evidence siRNA of ARF6/PLD2 with EM of ILVs and cargo controls (EGFR, HIV-1)

    PMID:24637612

    Open questions at the time
    • How ARF6/PLD2 lipids drive inward budding topologically unresolved
  13. 2015 High

    Explained how ARF6 drives invasion by coordinating JIP3/JIP4 with dynein-dynactin and kinesin-1 in a motor tug-of-war driving MT1-MMP endosome exocytosis.

    Evidence siRNA, Co-IP, live-cell endosome imaging, exocytosis and invasion assays

    PMID:26504170

    Open questions at the time
    • Quantitative balance of motor forces not measured
  14. 2015 High

    Demonstrated in vivo that endothelial ARF6 is required for HGF-stimulated β1-integrin recycling and tumor neoangiogenesis, with multiple GEFs and Grp1 as a druggable node.

    Evidence Endothelial-specific Arf6 conditional KO mice, recycling assays, tumor models, Grp1 inhibitor

    PMID:26239146

    Open questions at the time
    • Relative contributions of individual GEFs in vivo not separated
  15. 2016 High

    Linked ARF6 to lipid/cholesterol homeostasis by showing Arf6 loss elevates endosomal PI4P, disrupting SNX6/retromer retrograde transport of CI-M6PR and NPC2.

    Evidence Inducible Arf6 KO MEFs with PI4P, retromer tubulation, NPC2 and cholesterol readouts plus rescue

    PMID:27336679

    Open questions at the time
    • How ARF6 limits endosomal PI4P levels biochemically unresolved
  16. 2016 High

    Established physiological roles in hemostasis, showing platelet Arf6 controls αIIbβ3-mediated fibrinogen uptake, spreading and clot retraction.

    Evidence Platelet-specific Arf6 KO mice with fibrinogen uptake, spreading and clot retraction assays

    PMID:26738539

    Open questions at the time
    • GEF/GAP controlling platelet ARF6 not identified
  17. 2017 High

    Showed two GEFs route ARF6 to opposite VEGFR2 fates—ARNO to internalization, GEP100 to recycling—integrating signal output, with relevance to retinopathy.

    Evidence Conditional KO, biochemistry, pharmacology, and in vivo retinopathy models

    PMID:29058688

    Open questions at the time
    • How GEF choice is biased at a given receptor pool unclear
  18. 2019 High

    Defined a non-trafficking role: an ARF6-GTP/GRP1 shuttle captures pre-miRNA/Exportin-5 for delivery into tumor microvesicles, regulated by CK2 phosphorylation of RanGAP1.

    Evidence Co-IPs of ARF6-GTP/GRP1/Exportin-5/pre-miRNA with CK2 perturbation and TMV cargo quantification

    PMID:31235936

    Open questions at the time
    • How cytoplasmic ARF6-GTP intercepts the export complex spatially undefined
  19. 2019 High

    Established an in vivo neurodevelopmental role, showing Arf6 mediates Robo1 endocytosis/recycling for commissural axon midline crossing via a Slit-driven positive feedback loop.

    Evidence Arf6 KO mice, cytohesin dominant-negatives, Robo1 trafficking and in vivo axon guidance

    PMID:30674481

    Open questions at the time
    • Mechanism of feedback amplification not fully dissected
  20. 2022 High

    Reconstituted how ARF6 promotes exocyst-mediated tethering, recruiting PIP5K1C to generate PI(4,5)P2 that engages each exocyst subcomplex for membrane attachment.

    Evidence Reconstituted octameric exocyst, in vitro tethering and lipid binding, ARF6-PIP5K1C recruitment, cell validation

    PMID:35609603

    Open questions at the time
    • Direct ARF6-exocyst contacts vs. lipid-mediated recruitment not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse GEF/GAP repertoire, post-translational modifications, and lipid microenvironments are integrated to specify ARF6 activation at a precise location, time, and cargo remains unresolved.
  • No unified model of GEF/GAP selection per stimulus
  • Structural basis of ARF6 effector switching incompletely defined
  • In vivo cargo-specific recycling itineraries largely uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 5 GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005768 endosome 4 GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 3 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-9609507 Protein localization 4 R-HSA-1430728 Metabolism 3 R-HSA-1640170 Cell Cycle 3
Partners
ACAP1ARNOEFA6GEP100GRP1JIP3JIP4RHOB
Complex memberships
exocyst

Evidence

Reading pass · 59 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 ARF6 localizes to the endosomal/plasma membrane system (not the Golgi) and does not affect COP1 or γ-adaptin assembly on Golgi membranes. GTP hydrolysis-defective ARF6 localizes to the plasma membrane and induces extensive plasma membrane invaginations with depletion of endosomes; GTP-binding-defective ARF6 localizes exclusively to endosomal structures and causes accumulation of coated endocytic structures. Transient transfection of epitope-tagged ARF6 wild-type and GTPase mutants; immuno-electron microscopy; immunofluorescence The Journal of cell biology High 7896867
2001 ARF6 activates phosphatidylinositol 4-phosphate 5-kinase (PIP5K) to generate PIP2 at the plasma membrane and on tubular endosomal structures. PIP2 turnover controlled by the ARF6 GTP/GDP cycle is critical for membrane recycling through the ARF6 plasma membrane-endosomal pathway; constitutively active ARF6-Q67L traps PM proteins (β1-integrin, plakoglobin, MHCI) in PIP2-positive, actin-coated vacuoles unable to recycle. GFP-PH domain reporter for PIP2 localization; expression of ARF6 mutants and EFA6 exchange factor; fluorescence microscopy The Journal of cell biology High 11535619
2001 ARF6 associates with phospholipase D1 and PKCα upon Fcγ RI immune-complex aggregation; PLD1 lies upstream of all Fcγ RI-mediated PKC activity (PKCδ, ε, ζ translocation requires PLD1, not PKCα activity per se). ARF6 and PKCα form a complex with PLD1 to couple Fcγ RI to PLD1 activation. Co-immunoprecipitation; antisense oligonucleotide knockdown of PLD1; butan-1-ol phosphatidic acid assay; PKC translocation assays Current biology : CB Medium 11516649
2002 ARF6 redistributes to the cleavage furrow during telophase; ARF6-GTP levels transiently increase as cells progress through cytokinesis (measured by pull-down assay). Constitutively active ARF6 localizes to the plasma membrane at the cleavage furrow; dominant negative ARF6 remains cytoplasmic. Endogenous ARF6 immunofluorescence during mitosis; novel ARF6-GTP pull-down assay; expression of GTPase mutants The Journal of biological chemistry Medium 12016212
2003 ARF6 inactivation and acquisition of PI3P are required for convergence of non-clathrin endosomes with EEA1-positive early endosomes. Constitutively active ARF6-Q67L causes MHCI and Tac to accumulate in enlarged PIP2-enriched vacuoles and blocks their fusion with clathrin-cargo-containing endosomes and subsequent degradation, without affecting clathrin-cargo trafficking. Expression of ARF6 mutants; PI3-kinase inhibitor (wortmannin/LY294002); immunofluorescence; live-cell imaging Molecular biology of the cell Medium 12589044
2003 ARF6 regulates axonal elongation and branching through downstream activation of PI(4)P 5-kinase α. Catalytically inactive ARNO or dominant-negative ARF6 enhances axonal extension/branching; this effect is abrogated by constitutively active ARF6. PI(4)P 5-kinase α acts downstream of ARF6 in this pathway. ARF6 inactivation depletes Mena from growth cone leading edges. Expression of ARNO and ARF6 dominant mutants in cultured rat hippocampal neurons; genetic epistasis by co-expression; immunofluorescence for Mena Molecular biology of the cell Medium 14565977
2003 ARF6 regulates PIP2 formation at the phagocytic cup and activates PIP5K during β1-integrin-mediated bacterial (Yersinia) uptake. ARF6 defective for nucleotide binding reduces PIP2 around bound bacteria and impairs uptake. Overproduction of ARF6 or PIP5K can bypass the Rac1-GTP requirement for bacterial entry. Membrane-targeted PIP2 phosphatase expression; ARF6 dominant-negative mutant; PIP5K overexpression; Rac1 inactivation by YopE; bacterial invasion assay The Journal of experimental medicine Medium 12925676
2003 An initial ARF6-dependent decrease in Rac1-GTP is necessary for epithelial cell-cell dissociation during cell scattering; this is followed by coordinated increases in both ARF6 and Rac1 activation during cell migration. Active GTPase pull-down assays for endogenous ARF6-GTP and Rac1-GTP during sequential stages of HGF/scatter factor-induced MDCK cell scattering The Journal of biological chemistry Medium 12609992
2000 ACAP1 and ACAP2 are ARF6-specific GTPase-activating proteins (GAPs) that function in the cell periphery. In vitro, ACAP1 and ACAP2 have phosphoinositide-dependent GAP activity preferring ARF6 over ARF1 and ARF5. In cells, overexpression of ACAP1/2 blocks ARF6-dependent membrane protrusions; ACAP1/2 are recruited to peripheral tubular membranes where ARF6 activates for membrane recycling. In vitro GAP assay with purified proteins; ARF6-GTP competition; dominant mutant cell biology; immunofluorescence co-localization The Journal of cell biology High 11062263
2004 ARF6 localizes to invadopodia of breast cancer cells; siRNA-mediated suppression of ARF6 blocks invadopodia formation, localized matrix degradation, and Matrigel transmigration but not cell adhesion. Both GTP hydrolysis-defective (Q67L) and GTP-binding-defective (T27N) ARF6 mutants block invasion, demonstrating that continuous ARF6 GTPase cycling is required. siRNA knockdown; expression of GTPase mutants; invasion assays (Matrigel transmigration, matrix degradation); immunofluorescence Proceedings of the National Academy of Sciences of the United States of America High 15087504
2005 ARF6 is required for completion of cytokinesis. siRNA depletion of ARF6 disrupts the final stages of cytokinesis. Ku70, a DNA-binding protein, is identified as a new ARF6-interacting protein that forms a complex with ARF6 preferentially during mitosis. siRNA knockdown; co-immunoprecipitation; immunofluorescence during cell division Experimental cell research Medium 16181626
2005 ARF6 N-terminal α-helix is co-translationally myristoylated; both the helix and myristate affect nucleotide exchange, membrane association, and interaction with effector proteins. In vitro myristoylation; preparation and biochemical characterization of myristoylated Arf6 Methods in enzymology Medium 16413267
2006 V-ATPase a2-isoform on early endosomes interacts with ARNO in an intra-endosomal acidification-dependent manner; ARF6 interacts with the c-subunit of V-ATPase. Disruption of ARNO–V-ATPase interaction reversibly inhibits endocytosis and blocks protein trafficking from early to late endosomal compartments. Co-immunoprecipitation; pharmacological inhibition of endosomal acidification (bafilomycin); dominant-negative constructs; endocytosis assays Nature cell biology High 16415858
2006 BRAG2 (GEP100/Arf-GEP100) is a GEF that activates ARF6 in vivo. siRNA depletion of BRAG2 causes accumulation of β1-integrin on the cell surface and enhanced cell attachment/spreading on fibronectin. Conversely, siRNA depletion of ARF6 causes intracellular accumulation of β1-integrin and reduced adhesion, demonstrating that ARF6 regulates both endocytosis and recycling of β1-integrins. siRNA knockdown of BRAG2 and ARF6; β1-integrin surface and intracellular localization by immunofluorescence and flow cytometry; cell adhesion assay Current biology : CB High 16461286
2006 ARF6 and EFA6A regulate dendritic spine development and maintenance. Active ARF6 promotes spine formation from filopodia; EFA6A promotes spine formation in an ARF6 activation-dependent manner. siRNA knockdown of ARF6 or EFA6A decreases spine formation and reduces filopodia-to-spine conversion. ARF6 and EFA6A protect mature spines from inactivity-induced destabilization. siRNA knockdown; expression of dominant mutants; live-cell imaging; morphometric analysis of spine/filopodia ratio The Journal of neuroscience Medium 16672654
2006 A kinase-deficient TrkCT1 receptor binds scaffold protein tamalin in a ligand (NT3)-dependent manner; this complex activates ARF6 which in turn activates Rac1. NT3 triggers ARF6 membrane translocation, causing membrane ruffling and cellular protrusions. This identifies NT3 as an upstream regulator of ARF6. Co-immunoprecipitation; ARF6 membrane translocation imaging; dominant-negative mutants; Rac1 GTP pull-down The Journal of cell biology Medium 16636148
2006 ACAP4 is a novel ARF6-specific GAP with phosphatidylinositol 4,5-bisphosphate-dependent GAP activity. ACAP4 colocalizes with ARF6 at membrane ruffles upon EGF stimulation. Depletion of ACAP4 by siRNA or inhibition of ARF6 GTP hydrolysis suppresses ARF6-dependent cell migration in wound healing assays. Proteomic identification; in vitro GAP activity assay with PIP2 dependence; siRNA knockdown; co-localization; wound-healing migration assay Molecular & cellular proteomics : MCP High 16737952
2006 ARF6 activity is regulated during FcγR-mediated phagocytosis. ARF6 activation is restricted to the leading edge of the phagocytic cup. A PI3-kinase-dependent signal transition controls the sequential activation of ARF6 (early, cup leading edge) and ARF1 (delayed, over phagosome). PI3-K inhibition causes persistent ARF6 activation and minimal ARF1 activation. FRET stoichiometric microscopy of CFP/YFP-ARF chimeras and GTP-ARF binding domain; PI3-kinase pharmacological inhibition; phagocytosis assay PLoS biology High 16669702
2006 Dominant active ARF6 selectively activates PLD2 (not PLD1) in vivo. Dominant negative ARF6 selectively inhibits PLD2. ARF6 activates PLD2 in a cholesterol-dependent membrane microdomain. Co-localization of ARF6 and PLD isoforms was demonstrated at the cell periphery. Co-expression of ARF6 mutants with PLD1/PLD2 in HeLa cells; cell fractionation; methyl-β-cyclodextrin cholesterol depletion; PLD activity assay Journal of cellular biochemistry Medium 15759270
2006 TSHR (thyrotropin receptor) recycling relies on an hScrib-βPIX-GIT1-ARF6 pathway. ARF6 is activated during TSH stimulation of thyroid cells and is required for TSHR recycling. hScrib directly binds TSHR and associates with a βPIX-GIT1 complex; GIT1 (an ARF6 GAP) and ARF6 are both required for receptor recycling. Dominant-negative constructs; siRNA knockdown; TSHR recycling assay; ARF6 activation assay; co-immunoprecipitation The EMBO journal Medium 15775968
2007 ARF6 regulates angiotensin II type 1 receptor (AT1R) endocytosis by controlling recruitment of AP-2 and clathrin. ARF6-GDP binds β2-adaptin directly; ARF6-GTP preferentially binds clathrin heavy chain. ARF6 depletion prevents agonist-dependent recruitment of β2-adaptin and clathrin to activated AT1R and impairs β-arrestin 2 clustering. In vitro binding assays; co-immunoprecipitation; GFP-tagged adaptors; siRNA knockdown; AT1R endocytosis assay Cellular signalling Medium 17719203
2007 ARF6 activation downstream of Gαq: Gαq forms molecular complexes preferentially with activated ARNO and ARF6. Direct binding between purified Gαq and ARNO was demonstrated. Gαq-dependent TPβ receptor stimulation activates ARF6, leading to PIP2 production and TPβ receptor internalization. Co-immunoprecipitation; purified protein binding assay; ARF6 activation assay; PIP2 production assay; receptor internalization assay Cellular signalling Medium 16650966
2007 GULP (CED-6) is a positive regulator of ARF6. GULP binds GDP-bound ARF6 directly via its PTB domain, associates with the ARF6-GAP ACAP1, reverses ACAP1-mediated decrease in ARF6-GTP, and forms a tripartite GULP-ACAP1-ARF6-GDP complex that sequesters ACAP1, thereby increasing cellular ARF6-GTP levels. Co-immunoprecipitation of endogenous proteins; direct pulldown; siRNA knockdown; ARF6-GTP pull-down; cell migration assay Current biology : CB Medium 17398097
2007 ARF6-dependent tubulogenesis requires activation of ERK and subsequent Rac1 activation via ERK-induced upregulation of the urokinase plasminogen activator receptor (uPAR). ARF6 activation is necessary and sufficient to initiate tubule extension in 3D MDCK cultures and regulates subcellular distribution of Rac1 to tubule extensions. Inducible expression of ARF6 mutants; 3D cell culture (Matrigel); ERK activation assays; Rac1 distribution imaging The EMBO journal Medium 17363898
2007 Fbx8, an F-box protein containing a Sec7 domain, mediates ubiquitination of ARF6. This ubiquitination is not linked to immediate proteasomal degradation but renders ARF6 functionally inactive; Fbx8 knockdown causes ARF6 hyperactivation. Both F-box and Sec7 domains of Fbx8 are required to suppress ARF6 activity and tumor cell invasiveness. Co-immunoprecipitation; ubiquitination assay; siRNA knockdown; ARF6 activity assay; invasion assay; domain deletion mutants Molecular biology of the cell Medium 18094045
2007 CaSR (calcium-sensing receptor) stimulation induces plasma membrane ruffling via a β-arrestin-1/ARNO/ARF6/ELMO cascade. β-arrestin-1 co-immunoprecipitates with CaSR and ARNO; agonist treatment triggers co-translocation of CaSR, β-arrestin-1 and ARNO to membrane protrusions. ARF6 and ELMO are required for CaSR-dependent cytoskeletal reorganization. Co-immunoprecipitation; dominant-negative constructs; siRNA knockdown; immunofluorescence co-localization at membrane ruffles Journal of cell science Medium 17623778
2008 ARF6 is required for dendritic cell podosome formation and migration. Expression of either Q67L (GTP-locked) or T44N (GDP-locked) ARF6 mutants strongly inhibits F-actin-rich podosome formation and impairs immature DC migration toward CCL3. LPS-stimulated macropinocytosis is suppressed by Q67L ARF6. Retroviral expression of ARF6 mutants in primary murine dendritic cells; F-actin podosome quantification; migration assay toward chemokines European journal of immunology Medium 18286566
2009 ARF6 GTP/GDP cycle regulates the release of protease-loaded plasma membrane-derived microvesicles from tumor cells. Mechanistically: ARF6-GTP activates phospholipase D, which recruits ERK to the plasma membrane; ERK phosphorylates and activates MLCK; MLCK-mediated MLC phosphorylation is required for microvesicle release. PKC-mediated MLC phosphorylation (downstream of ARF6 inhibition) blocks shedding. ARF6 mutant expression; PLD inhibition; ERK inhibition; MLCK inhibition; MLC phosphorylation assay; microvesicle quantification Current biology : CB High 19896381
2009 EGFR activates ARF6 through the GEF GEP100 in breast cancer cells to promote invasion and metastasis via the EGFR-GEP100-ARF6-AMAP1 pathway. GEP100 directly binds ligand-activated EGFR. Both ARF6 and AMAP1 must be highly overexpressed and EGFR must be ligand-activated for full invasion pathway activation. Co-immunoprecipitation of GEP100 with EGFR; siRNA knockdowns; ARF6 activity assay; Matrigel invasion assay Traffic (Copenhagen, Denmark) Medium 19416474
2009 EphA2, upon ligand activation by ephrin-A, suppresses ARF6 activity through a Nck1-Git1 signaling pathway. Ligand-activated EphA2 via phospho-Tyr594 binds Nck1 SH2 domain; Nck1 SH3 domain binds Git1 synaptic localizing domain; Git1 then suppresses ARF6. This suppression promotes cell compaction and polarization, enhancing E-cadherin-based cell-cell contacts. ARF6 activity assay; co-immunoprecipitation; phospho-tyrosine mutant EphA2; domain-specific mutants; cell compaction/polarity assay Molecular biology of the cell Medium 19193766
2010 TBC1D24 binds ARF6 (co-immunoprecipitation). TBC1D24 overexpression increases neurite length and arborization; FIME disease mutations (D147H, A509V) significantly revert this phenotype, implicating the ARF6-dependent pathway in brain hyperexcitability. Co-immunoprecipitation; TBC1D24 overexpression and disease mutant expression; neurite morphometry in neurons American journal of human genetics Medium 20727515
2010 Activated H-Ras induces methuosis via downstream activation of Rac1 combined with reciprocal inactivation of ARF6. Rac1 activation by H-Ras(G12V) decreases ARF6-GTP; this is mediated by Rac1 stimulation of the ARF6-GAP GIT1. Constitutively active Rac1 interacts with GIT1 by co-immunoprecipitation; shRNA ablation of GIT1 prevents ARF6 inactivation and vacuolization. ARF6-GTP and Rac1-GTP pull-down assays; shRNA knockdown of GIT1; Rac1 inhibitor EHT 1864; co-immunoprecipitation; vacuolization scoring Molecular cancer research : MCR Medium 20713492
2011 GEP100/Brag2 mediates Sema3E-induced ARF6 activation in endothelial cells downstream of Plexin-D1. Upon Sema3E activation, Plexin-D1 recruits PI4P5-kinase; its product PI(4,5)P2 binds the PH domain of GEP100, enhancing its GEF activity toward ARF6, leading to disassembly of integrin-mediated focal adhesions. Co-immunoprecipitation of Plexin-D1 with PIP5K; PH domain PIP2-binding assay; ARF6 activity assay; focal adhesion disassembly imaging; dominant-negative GEP100 The Journal of biological chemistry Medium 21795701
2011 VEGFR2 recruits GEP100 to activate ARF6, and the GEP100-ARF6-AMAP1-cortactin pathway is essential for VEGF-induced angiogenesis activities (cell migration, tube formation, permeability enhancement, VE-cadherin endocytosis). Co-immunoprecipitation; siRNA knockdowns; ARF6 activity assay; tube formation and migration assays; VE-cadherin endocytosis assay PloS one Medium 21858086
2011 ARF6 negatively regulates Rab35 activation by using EPI64B as an effector. EPI64B is a Rab35-GAP that functions as an ARF6 effector. Constitutively active ARF6 reduces Rab35 loading into the endocytic pathway at clathrin-coated pits, causing endocytic recycling and cytokinesis defects identical to those of inactivated Rab35. Expression of constitutively active ARF6-Q67L; identification of EPI64B as ARF6 effector; Rab35-GTP levels; endocytic recycling assay; cytokinesis defect scoring Current biology : CB High 22226746
2011 ARF6-GTP associates with clathrin-coated pits (CCPs) at the plasma membrane in an AP-2-dependent mechanism. In CCPs, ARF6-GTP mediates recruitment of JIP3 and JIP4 effectors after auxilin recruitment. ARF6 does not contribute to receptor-mediated clathrin-dependent endocytosis but instead ARF6-JIP interaction on endocytic vesicles is required for fast microtubule-dependent recycling of the transferrin receptor. TIRF microscopy of GFP-ARF6; AP-2 mutant analysis; ARF6-JIP interaction assays; transferrin receptor recycling assay Current biology : CB High 21439824
2012 IL-1β signals through a NF-κB-independent MYD88-ARNO-ARF6 pathway to disrupt endothelial barrier function. ARNO binds directly to MYD88; this interaction activates ARF6, which disrupts endothelial cell-cell junctions. The ARF6-GEF inhibitor SecinH3 enhances vascular stability and improves outcomes in animal models of inflammatory arthritis and acute inflammation. Direct binding assay (MYD88-ARNO); ARF6 activation assay; dominant-negative constructs; SecinH3 pharmacological inhibition; in vitro permeability assay; in vivo inflammatory models Nature High 23143332
2012 Rab35 suppresses ARF6 activity to maintain cadherins at the cell surface and inhibit cell migration. Rab35 knockdown de-represses ARF6, leading to increased β1-integrin and EGF receptor recycling and decreased E-cadherin at the surface, promoting an EMT-like state. siRNA knockdown of Rab35; ARF6 activity assay; β1-integrin and cadherin surface quantification; migration assay Journal of cell science Medium 23264734
2012 ARF6 directs rapid axonal transport of α9β1 integrins in ARF6-positive vesicles. ARF6 inactivation (ACAP1 expression) increases β1 integrin recycling to the neuronal surface and increases anterograde axonal transport; ARF6 activation (ARNO or EFA6 expression) increases retrograde integrin transport and internalization. ARF6 inactivation increases integrin-mediated axon outgrowth. Live-cell imaging of integrin-GFP vesicles in DRG axons and PC12 cells; ACAP1, ARNO, EFA6 overexpression; integrin surface quantification; neurite outgrowth assay The Journal of neuroscience Medium 22836268
2013 AGAP3 is a component of the NMDA receptor complex and regulates NMDA receptor-mediated Ras/ERK and ARF6 signaling pathways during chemically induced LTP. AGAP3 knockdown occludes AMPA receptor trafficking during LTP, establishing AGAP3 as a link between NMDA receptor activation and ARF6-dependent AMPA receptor trafficking. Co-immunoprecipitation with NMDA receptor complex; siRNA knockdown; ARF6 activity assay; AMPA receptor trafficking assay during chemically-induced LTP in rat neurons The Journal of neuroscience Medium 23904596
2014 ARF6 and its effector PLD2 control syntenin exosome biogenesis by regulating budding of intraluminal vesicles (ILVs) into multivesicular bodies (MVBs). ARF6 also controls EGF receptor degradation but does not affect HIV-1 budding, excluding a general effect on ESCRT. siRNA knockdown of ARF6 and PLD2; electron microscopy of MVBs and ILVs; exosome quantification; EGFR degradation assay; HIV-1 budding assay Nature communications High 24637612
2015 ARF6 together with JIP3 and JIP4 effectors regulates MT1-MMP exocytosis for cancer cell invasion. JIPs are recruited by WASH on MT1-MMP endosomes and recruit dynein-dynactin and kinesin-1. Plasma membrane ARF6 interacts with endosomal JIPs to coordinate dynein-dynactin and kinesin-1 in a tug-of-war that drives MT1-MMP endosome tubulation and exocytosis. ARF6 or JIP3/4 silencing mispositiones MT1-MMP endosomes and reduces exocytosis and invasion. siRNA silencing; co-immunoprecipitation; live-cell imaging of MT1-MMP endosomes; MT1-MMP exocytosis assay; Matrigel invasion assay The Journal of cell biology High 26504170
2015 Endothelial-specific deletion of ARF6 abolishes HGF-stimulated β1-integrin recycling and suppresses tumor neoangiogenesis and growth. GEFs GEP100, EFA6B, EFA6D, and Grp1 regulate HGF-stimulated β1-integrin recycling; pharmacological inhibition of the ARF6 GEF Grp1 suppresses tumor vascularization. Conditional endothelial-specific Arf6 knockout mice; β1-integrin recycling assay; tumor implantation model; Grp1 inhibitor pharmacology Nature communications High 26239146
2016 Arf6 controls retromer trafficking via a phosphoinositide-based mechanism. Arf6 KO MEFs accumulate free cholesterol in late endosomes/lysosomes due to mistrafficking of NPC2, a cargo of CI-M6PR. This results from a selective increase in endosomal PI4P that perturbs retromer-mediated retrograde transport of CI-M6PR via SNX6 (a PI4P effector). Reducing PI4P in KO MEFs rescues retromer tubulation and cholesterol distribution. Inducible Arf6 knockout MEFs; PI4P immunofluorescence and quantification; retromer tubulation imaging; NPC2 trafficking assay; cholesterol staining; PI4P manipulation Nature communications High 27336679
2016 Arf6 controls platelet spreading and clot retraction via αIIbβ3 integrin trafficking. Arf6 KO platelets show reduced fibrinogen (Fg) uptake, deficient FITC-Fg internalization, enhanced spreading on Fg, and faster clot retraction, without changes in resting/activated αIIbβ3 levels, MLC phosphorylation, or Rac1/RhoA activation. Platelet-specific Arf6 conditional KO mice; biotinylated/FITC-Fg uptake in vivo and ex vivo; flow cytometry; immunofluorescence of Rab4/Rab11 vesicles; clot retraction assay Blood High 26738539
2016 LPA activates ARF6 via G-protein-coupled LPA receptors through GTP-Gα12 binding to EFA6 in renal cancer cells, promoting mesenchymal invasion. This is distinct from the GEP100-mediated activation seen in breast cancer cells. ARF6 activity assay; LPA stimulation; Gα12 dominant-negative; EFA6 co-immunoprecipitation; invasion assay Nature communications Medium 26854204
2016 The mevalonate pathway enzyme GGT-II and its substrate Rab11b are required for ARF6 trafficking to the plasma membrane for activation by receptor tyrosine kinases. Mutant p53 promotes ARF6 activation by supporting GGT-II and Rab11b. MVP inhibition blocked invasion and metastasis only in cells overexpressing ARF6. GGT-II inhibitor; Rab11b siRNA; ARF6 plasma membrane localization imaging; invasion and metastasis assays; ARF6 activation assay The Journal of cell biology Medium 27044891
2017 ARF6 controls VEGFR2 trafficking and signaling through two distinct GEFs: ARNO activates ARF6 to promote VEGFR2 internalization; GEP100 activates ARF6 to promote VEGFR2 recycling via coreceptor binding. Both pathways converge to determine VEGFR2 signal output and are targets for diabetic retinopathy intervention. In vitro, cellular, genetic (conditional KO), and pharmacological approaches; VEGFR2 trafficking assay; ARF6 activation assay; ARNO and GEP100 interaction with VEGFR2; in vivo retinopathy models The Journal of clinical investigation High 29058688
2018 The Arf6-AMAP1 pathway promotes anterograde trafficking of mitochondria by promoting ILK localization to focal adhesions, thereby blocking RhoT1-TRAK2 (retrograde) association. This is required for avoiding detrimental ROS production during cell invasion. siRNA and dominant-mutant blocking of Arf6-AMAP1 pathway; mitochondria localization imaging; ROS measurement; ILK-focal adhesion immunofluorescence; TRAK1/2 co-immunoprecipitation with RhoT1; invasion assay Nature communications Medium 29992963
2018 Microexon switching in the ARF6 GEF cytohesin-1 controls Met-dependent cell migration. Diglycine (microexon-skipped) isoform has differential affinity for PI(3,4,5)P3 vs. triglycine isoform (PI(4,5)P2), directing distinct subcellular localizations—triglycine to plasma membrane, diglycine to leading edge—thereby spatially restricting ARF6 activation and downstream HGF/Met-dependent migration. Phosphoinositide-binding assay; subcellular localization imaging; Met receptor co-immunoprecipitation; microexon isoform rescue; cell migration assay The Journal of cell biology Medium 30404949
2019 ARF6-GTP forms a cytoplasmic shuttle with GRP1 that captures pre-miRNA/Exportin-5 complex following Ran-GTP dissociation after nuclear export, delivering pre-miRNA cargo to nascent tumor microvesicles. ARF6 activation increases pre-miRNA content in TMVs through a process requiring casein kinase 2-mediated phosphorylation of RanGAP1. Co-immunoprecipitation of ARF6-GTP, GRP1, Exportin-5, pre-miRNA; ARF6 activation manipulation; CK2 inhibition/mutation; TMV pre-miRNA quantification Nature cell biology High 31235936
2019 Arf6 is required for commissural axon midline crossing; Slit-Robo1 signaling activates Arf6 via cytohesins. Arf6 mediates endocytosis and recycling of Robo1 receptor, which maintains receptor stability during Slit stimulation. A positive feedback loop is established: Robo1 endocytosis triggers Arf6-mediated amplification of Slit response. Arf6-knockout mice (commissural axon phenotype); cytohesin dominant-negative; Robo1 endocytosis/recycling assay; ARF6 activation assay; in vivo axon guidance imaging Development (Cambridge, England) High 30674481
2019 ARF6 forms a complex with RhoB; the GCI residues (188-190) of RhoB mediate this interaction. Targeting ARF6 to plasma membrane or mitochondrial membranes promotes co-recruitment of RhoB. ARF6 depletion causes RhoB loss from endosomal membranes and RhoB degradation via an endolysosomal pathway, resulting in defective actin and focal adhesion dynamics. Co-immunoprecipitation; ARF6 targeted to specific membranes; confocal imaging of RhoB localization; ARF6 KD; RhoB degradation assay; focal adhesion imaging The Journal of cell biology Medium 31591185
2019 Arf6 and macropinocytosis machinery (JIP3, dynein) shape macropinosome formation and inward movement. Arf6 and JIP3 (a microtubule motor scaffold/ARF6 effector) are required for sealing and transport of macropinosomes through the actin-myosin-rich lamellar region along microtubule tracks. siRNA knockdown of Arf6, JIP3, dynein; live-cell imaging of macropinosome formation and transport; microtubule depolymerization Molecular biology of the cell Medium 30969891
2019 KRAS promotes ARF6 mRNA translation through eIF4A-dependent mechanism involving a G-quadruplex structure in the 5'-UTR of ARF6 mRNA, by inducing TEAD3 and ETV4 to suppress PDCD4. TP53 facilitates ARF6 activation by PDGF via promoting PDGFRβ expression and mevalonate pathway enzymes. Translational reporter for ARF6 5'-UTR; eIF4A inhibitor silvestrol; PDCD4 knockdown; ARF6 activity assay upon PDGF stimulation; KPC mouse model Proceedings of the National Academy of Sciences of the United States of America Medium 31399545
2022 N-myristoylated ARF6 recognizes palmitoylated EGFR via lipid-lipid interaction, recruits the exocyst complex to promote EGFR budding from the Golgi, and facilitates EGFR transport to the plasma membrane in its GTP-bound form. DHHC13 palmitoylates EGFR, which is critical for plasma membrane localization. Co-immunoprecipitation; lipid-lipid interaction assay; EGFR palmitoylation assay (DHHC13 identification); exocyst recruitment assay; plasma membrane EGFR localization; cell-permeable peptide (GKVL-TAT) disrupting this interaction Nature communications Medium 36224181
2022 ARF6-mediated recruitment of PIP5K1C converts PI(4)P to PI(4,5)P2 on late-stage vesicles near the plasma membrane, driving exocyst recruitment and membrane tethering. Reconstitution of functional octameric human exocyst demonstrated that each subcomplex independently binds PI(4,5)P2 for membrane tethering. Reconstitution of functional octameric exocyst; in vitro membrane tethering assay; PI(4,5)P2 binding assay; ARF6-PIP5K1C membrane recruitment experiment; epithelial cell biology validation Current biology : CB High 35609603
2022 DDR1 activates ARF6 by recruiting the GEF PSD4 in a collagen-stimulated, DDR1 kinase-dependent manner in hepatocellular carcinoma cells. DDR1 physically interacts with ARF6 (co-immunoprecipitation). DDR1 kinase activity is required for ARF6 activation. Co-immunoprecipitation; kinase-dead DDR1 mutant; ARF6 activity assay; PSD4 recruitment assay; invasion and metastasis assays Oncogene Medium 35140331
2023 LRRK2-hyperphosphorylated RABs disrupt autophagosome axonal transport by disrupting coordinated regulation of dynein and kinesin. ARF6 overexpression attenuates transport defects in LRRK2-p.R1441H knockin and PPM1H knockout neurons, acting as a switch for selective activation of dynein or kinesin. iPSC-derived human neurons with LRRK2-p.R1441H knockin; PPM1H knockout; ARF6 overexpression rescue; live-cell imaging of autophagosome transport Cell reports Medium 37133994

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Current biology : CB 698 19896381
2005 Auxin response factors ARF6 and ARF8 promote jasmonic acid production and flower maturation. Development (Cambridge, England) 509 16107481
2014 Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2. Nature communications 456 24637612
2006 V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway. Nature cell biology 396 16415858
2001 Phosphatidylinositol 4,5-bisphosphate and Arf6-regulated membrane traffic. The Journal of cell biology 375 11535619
1995 Overexpression of wild-type and mutant ARF1 and ARF6: distinct perturbations of nonoverlapping membrane compartments. The Journal of cell biology 333 7896867
2003 Convergence of non-clathrin- and clathrin-derived endosomes involves Arf6 inactivation and changes in phosphoinositides. Molecular biology of the cell 235 12589044
2004 Requirement for Arf6 in breast cancer invasive activities. Proceedings of the National Academy of Sciences of the United States of America 222 15087504
2000 ACAPs are arf6 GTPase-activating proteins that function in the cell periphery. The Journal of cell biology 169 11062263
2003 ARNO and ARF6 regulate axonal elongation and branching through downstream activation of phosphatidylinositol 4-phosphate 5-kinase alpha. Molecular biology of the cell 141 14565977
2012 Interleukin receptor activates a MYD88-ARNO-ARF6 cascade to disrupt vascular stability. Nature 140 23143332
2010 TBC1D24, an ARF6-interacting protein, is mutated in familial infantile myoclonic epilepsy. American journal of human genetics 131 20727515
2012 An ARF6/Rab35 GTPase cascade for endocytic recycling and successful cytokinesis. Current biology : CB 129 22226746
2010 ARF6-mediated endocytic recycling impacts cell movement, cell division and lipid homeostasis. Seminars in cell & developmental biology 126 20837153
2019 ARF6 and AMAP1 are major targets of KRAS and TP53 mutations to promote invasion, PD-L1 dynamics, and immune evasion of pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America 119 31399545
2019 An ARF6-Exportin-5 axis delivers pre-miRNA cargo to tumour microvesicles. Nature cell biology 114 31235936
2015 ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion. The Journal of cell biology 110 26504170
2012 Interplay between Rab35 and Arf6 controls cargo recycling to coordinate cell adhesion and migration. Journal of cell science 106 23264734
2006 The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling endocytosis of beta1 integrins. Current biology : CB 101 16461286
2006 A phosphatidylinositol-3-kinase-dependent signal transition regulates ARF1 and ARF6 during Fcgamma receptor-mediated phagocytosis. PLoS biology 100 16669702
2009 The EGFR-GEP100-Arf6-AMAP1 signaling pathway specific to breast cancer invasion and metastasis. Traffic (Copenhagen, Denmark) 98 19416474
2003 Requirement for Arf6 in cell adhesion, migration, and cancer cell invasion. Journal of biochemistry 96 14607973
2002 Localization and activation of the ARF6 GTPase during cleavage furrow ingression and cytokinesis. The Journal of biological chemistry 94 12016212
2006 ARF6 and EFA6A regulate the development and maintenance of dendritic spines. The Journal of neuroscience : the official journal of the Society for Neuroscience 91 16672654
2016 Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer. Nature communications 88 26854204
2020 Abrogation of ARF6 promotes RSL3-induced ferroptosis and mitigates gemcitabine resistance in pancreatic cancer cells. American journal of cancer research 82 32368394
2010 Induction of nonapoptotic cell death by activated Ras requires inverse regulation of Rac1 and Arf6. Molecular cancer research : MCR 82 20713492
2012 ARF6 directs axon transport and traffic of integrins and regulates axon growth in adult DRG neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 79 22836268
2003 Modulation of Rac1 and ARF6 activation during epithelial cell scattering. The Journal of biological chemistry 78 12609992
2017 Roles of Arf6 in cancer cell invasion, metastasis and proliferation. Life sciences 75 28625359
2006 A kinase-deficient TrkC receptor isoform activates Arf6-Rac1 signaling through the scaffold protein tamalin. The Journal of cell biology 73 16636148
2003 Arf6 and phosphoinositol-4-phosphate-5-kinase activities permit bypass of the Rac1 requirement for beta1 integrin-mediated bacterial uptake. The Journal of experimental medicine 72 12925676
2018 Arf6-driven cell invasion is intrinsically linked to TRAK1-mediated mitochondrial anterograde trafficking to avoid oxidative catastrophe. Nature communications 69 29992963
2019 The Small GTPase Arf6: An Overview of Its Mechanisms of Action and of Its Role in Host⁻Pathogen Interactions and Innate Immunity. International journal of molecular sciences 68 31060328
2007 Mucolipin-2 localizes to the Arf6-associated pathway and regulates recycling of GPI-APs. Traffic (Copenhagen, Denmark) 68 17662026
2005 Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway. The EMBO journal 64 15775968
2009 EphA2 engages Git1 to suppress Arf6 activity modulating epithelial cell-cell contacts. Molecular biology of the cell 61 19193766
2016 Arf6 controls platelet spreading and clot retraction via integrin αIIbβ3 trafficking. Blood 58 26738539
2013 AGAP3 and Arf6 regulate trafficking of AMPA receptors and synaptic plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 58 23904596
2015 Arf6 regulates tumour angiogenesis and growth through HGF-induced endothelial β1 integrin recycling. Nature communications 57 26239146
2011 GEP100-Arf6-AMAP1-cortactin pathway frequently used in cancer invasion is activated by VEGFR2 to promote angiogenesis. PloS one 57 21858086
2011 Regulation of PIP5K activity by Arf6 and its physiological significance. Journal of cellular physiology 56 20945365
2011 Decoupling of activation and effector binding underlies ARF6 priming of fast endocytic recycling. Current biology : CB 54 21439824
2005 A requirement for ARF6 during the completion of cytokinesis. Experimental cell research 54 16181626
2016 P53- and mevalonate pathway-driven malignancies require Arf6 for metastasis and drug resistance. The Journal of cell biology 52 27044891
2015 The Role of ARF6 in Biliary Atresia. PloS one 51 26379158
2007 ARF6-dependent activation of ERK and Rac1 modulates epithelial tubule development. The EMBO journal 51 17363898
2019 CLIC4/Arf6 Pathway. Circulation research 48 30582444
2006 Proteomic identification and functional characterization of a novel ARF6 GTPase-activating protein, ACAP4. Molecular & cellular proteomics : MCP 46 16737952
2017 Small GTPase ARF6 controls VEGFR2 trafficking and signaling in diabetic retinopathy. The Journal of clinical investigation 45 29058688
2016 Arf6 controls retromer traffic and intracellular cholesterol distribution via a phosphoinositide-based mechanism. Nature communications 44 27336679
2022 DDR1 promotes hepatocellular carcinoma metastasis through recruiting PSD4 to ARF6. Oncogene 43 35140331
2022 Targeting EGFR-dependent tumors by disrupting an ARF6-mediated sorting system. Nature communications 43 36224181
2011 Phosphatidylinositol-4-phosphate 5-kinase and GEP100/Brag2 protein mediate antiangiogenic signaling by semaphorin 3E-plexin-D1 through Arf6 protein. The Journal of biological chemistry 43 21795701
2017 Tissue Factor Prothrombotic Activity Is Regulated by Integrin-arf6 Trafficking. Arteriosclerosis, thrombosis, and vascular biology 42 28495929
2014 ARF6 inhibition stabilizes the vasculature and enhances survival during endotoxic shock. Journal of immunology (Baltimore, Md. : 1950) 42 24835390
2005 Preparation of myristoylated Arf1 and Arf6. Methods in enzymology 41 16413267
2019 Arf6, JIP3, and dynein shape and mediate macropinocytosis. Molecular biology of the cell 40 30969891
2013 Arf6, Rab11 and transferrin receptor define distinct populations of recycling endosomes. Communicative & integrative biology 40 24255739
2007 The calcium-sensing receptor changes cell shape via a beta-arrestin-1 ARNO ARF6 ELMO protein network. Journal of cell science 40 17623778
2022 A mechanism for exocyst-mediated tethering via Arf6 and PIP5K1C-driven phosphoinositide conversion. Current biology : CB 36 35609603
2002 ARF6: a newly appreciated player in G protein-coupled receptor desensitization. FEBS letters 36 12067715
2016 The small GTPase ARF6 regulates protein trafficking to control cellular function during development and in disease. Small GTPases 34 28001501
2019 Arf6-driven endocytic recycling of CD147 determines HCC malignant phenotypes. Journal of experimental & clinical cancer research : CR 33 31752956
2018 MiR-145 improves macrophage-mediated inflammation through targeting Arf6. Endocrine 33 29388044
2011 Distinct roles of Rab11 and Arf6 in the regulation of Rab11-FIP3/arfophilin-1 localization in mitotic cells. Genes to cells : devoted to molecular & cellular mechanisms 33 21790911
2007 ARF6 regulates angiotensin II type 1 receptor endocytosis by controlling the recruitment of AP-2 and clathrin. Cellular signalling 33 17719203
2001 Crosstalk between ARF6 and protein kinase Calpha in Fc(gamma)RI-mediated activation of phospholipase D1. Current biology : CB 33 11516649
2008 A role for ARF6 in dendritic cell podosome formation and migration. European journal of immunology 32 18286566
2022 CCL18 promotes breast cancer progression by exosomal miR-760 activation of ARF6/Src/PI3K/Akt pathway. Molecular therapy oncolytics 31 35399607
2015 Arf6 controls beta-amyloid production by regulating macropinocytosis of the Amyloid Precursor Protein to lysosomes. Molecular brain 31 26170135
2023 Regulatory imbalance between LRRK2 kinase, PPM1H phosphatase, and ARF6 GTPase disrupts the axonal transport of autophagosomes. Cell reports 30 37133994
2016 Pathological functions of the small GTPase Arf6 in cancer progression: Tumor angiogenesis and metastasis. Small GTPases 29 26909552
2005 Localization and regulation of phospholipase D2 by ARF6. Journal of cellular biochemistry 29 15759270
2003 Differential expression and targeting of endogenous Arf1 and Arf6 small GTPases in kidney epithelial cells in situ. American journal of physiology. Cell physiology 29 14684384
2007 Regulation of Arf6 and ACAP1 signaling by the PTB-domain-containing adaptor protein GULP. Current biology : CB 28 17398097
2013 ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology. The Journal of biological chemistry 27 23295182
2007 Fbx8 makes Arf6 refractory to function via ubiquitination. Molecular biology of the cell 27 18094045
2006 ARF6 activation by Galpha q signaling: Galpha q forms molecular complexes with ARNO and ARF6. Cellular signalling 27 16650966
2011 Rac1 and calmodulin interactions modulate dynamics of ARF6-dependent endocytosis. Traffic (Copenhagen, Denmark) 26 21883766
2022 Abrogation of ARF6 in promoting erastin-induced ferroptosis and mitigating capecitabine resistance in gastric cancer cells. Journal of gastrointestinal oncology 25 35837166
2019 A crucial role for Arf6 in the response of commissural axons to Slit. Development (Cambridge, England) 25 30674481
2011 Inhibition of cell migration by PITENINs: the role of ARF6. Oncogene 25 22179837
2012 ARF6-dependent regulation of P2Y receptor traffic and function in human platelets. PloS one 24 22916275
2011 Macropinocytosis inhibitors and Arf6 regulate ErbB3 nuclear localization in prostate cancer cells. Molecular carcinogenesis 24 21438025
2023 Platelet-derived extracellular vesicles aggravate septic acute kidney injury via delivering ARF6. International journal of biological sciences 23 37928258
2021 Inhibition of mutant KRAS-driven overexpression of ARF6 and MYC by an eIF4A inhibitor drug improves the effects of anti-PD-1 immunotherapy for pancreatic cancer. Cell communication and signaling : CCS 23 34001163
2019 Small GTPase Arf6 regulates diabetes-induced cholesterol accumulation in podocytes. Journal of cellular physiology 23 31206670
2019 Arf6 regulates RhoB subcellular localization to control cancer cell invasion. The Journal of cell biology 23 31591185
2018 HGF-induced migration depends on the PI(3,4,5)P3-binding microexon-spliced variant of the Arf6 exchange factor cytohesin-1. The Journal of cell biology 23 30404949
2017 Arf6 and Rab22 mediate T cell conjugate formation by regulating clathrin-independent endosomal membrane trafficking. Journal of cell science 23 28584192
2008 ARF6, PI3-kinase and host cell actin cytoskeleton in Toxoplasma gondii cell invasion. Biochemical and biophysical research communications 23 19061866
2020 MicroRNA-145 suppresses cell migration and invasion in upper tract urothelial carcinoma by targeting ARF6. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22 32077148
2020 Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway. PloS one 22 32119711
2018 Sphingolipids inhibit endosomal recycling of nutrient transporters by inactivating ARF6. Journal of cell science 22 29848659
2004 Regulation of G protein-coupled receptor endocytosis by ARF6 GTP-binding proteins. Biochemistry and cell biology = Biochimie et biologie cellulaire 22 15674428
2021 Arf6 exacerbates allergic asthma through cell-to-cell transmission of ASC inflammasomes. JCI insight 21 34423792
2020 High expression of AMAP1, an ARF6 effector, is associated with elevated levels of PD-L1 and fibrosis of pancreatic cancer. Cell communication and signaling : CCS 21 32580737
2018 RAB-35 and ARF-6 GTPases Mediate Engulfment and Clearance Following Linker Cell-Type Death. Developmental cell 21 30220571
2014 Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2. Biochemical pharmacology 21 25450674

Missed literature

Know a paper Affinage missed for ARF6? Flag it for the maintainers and the community.

No submissions yet.