Affinage

ARFGEF2

Brefeldin A-inhibited guanine nucleotide-exchange protein 2 · UniProt Q9Y6D5

Length
1785 aa
Mass
202.0 kDa
Annotated
2026-04-28
40 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARFGEF2 (BIG2) is a brefeldin A-sensitive guanine nucleotide-exchange factor that activates class I ARFs (ARF1, ARF3) at the trans-Golgi network and recycling endosomes to drive vesicle coat recruitment, cargo trafficking, and organelle integrity. At the TGN, BIG2 specifically promotes AP-1 and GGA coat protein association (but not COPI) to mediate anterograde and retrograde transport of cargoes including E-cadherin, β-catenin, integrin β1, Filamin A, and TNFR1-containing exosome-like vesicles; at recycling endosomes, it maintains compartment structure and supports transferrin receptor recycling through ARF1/ARF3 activation (PMID:11777925, PMID:12051703, PMID:15385626, PMID:16477018, PMID:22908276). BIG2 also functions as a multi-domain AKAP scaffold that anchors PKA regulatory subunits (RIα, RIIβ) and PP1γ, coupling cAMP/PKA signaling to regulation of its own GEF activity and to β-catenin phosphorylation-dependent transcriptional co-activation, and independently of catalytic activity scaffolds myosin phosphatase complexes to control actin dynamics and directed cell migration (PMID:12571360, PMID:17360629, PMID:18625701, PMID:23918382, PMID:27162341). In neurons, BIG2 signals through an ARF1→RhoA→mDia1 axis to polarize dendritic Golgi outposts and support dendrite morphogenesis, and loss-of-function mutations cause the autosomal recessive brain malformation periventricular heterotopia with microcephaly (PMID:14647276, PMID:29455446).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    BIG2 was placed specifically in TGN-to-endosome trafficking by showing it recruits AP-1 and GGA coat proteins—but not COPI—to TGN membranes through ARF activation, resolving which coat pathways depend on this GEF.

    Evidence BIG2 overexpression and dominant-negative mutant expression with immunofluorescence for AP-1, GGA1, and COPI in mammalian cells

    PMID:11777925 PMID:12051703

    Open questions at the time
    • Direct binding between BIG2 and coat adaptors not demonstrated
    • Cargo specificity of BIG2 versus BIG1 at TGN not resolved
  2. 2003 High

    BIG2 was identified as a dual-function molecule—an ARF-GEF and an AKAP scaffold—with three distinct PKA regulatory subunit-binding domains, establishing a direct link between cAMP/PKA signaling and vesicular trafficking machinery.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation of endogenous RIα, deletion mapping of AKAP domains A/B/C, subcellular fractionation showing cAMP-induced membrane translocation

    PMID:12571360

    Open questions at the time
    • Functional consequences of PKA binding for ARF activation not yet tested
    • Which AKAP domain is most physiologically relevant unclear
  3. 2003 High

    ARFGEF2 mutations were linked to periventricular heterotopia with microcephaly, and BIG2 inhibition was shown to disrupt E-cadherin/β-catenin surface transport in neural progenitors, connecting vesicle trafficking to brain development.

    Evidence Human genetic analysis, dominant-negative ARFGEF2 cDNA transfection, BFA treatment, immunofluorescence in neural cell lines

    PMID:14647276

    Open questions at the time
    • Precise cargo sorting step affected in neural progenitors not defined
    • Whether E-cadherin mislocalization is sufficient to explain the human malformation not tested
  4. 2004 High

    BIG2 was shown to localize to recycling endosomes in addition to TGN and to activate ARF1 and ARF3 specifically, with catalytic-dead mutant and ARF knockdown epistasis demonstrating that BIG2 maintains recycling endosome structural integrity through class I ARF activation.

    Evidence E738K catalytic mutant expression, ARF1/ARF3 knockdown, organelle morphology analysis

    PMID:15385626

    Open questions at the time
    • Mechanism by which ARF-GTP maintains endosomal membrane stability not resolved
    • Whether BIG2 acts on ARF1 and ARF3 sequentially or independently unknown
  5. 2006 High

    BIG2 was shown to have non-redundant endosomal functions distinct from BIG1: BIG2 specifically supports transferrin receptor recycling from endosomes, while expression studies placed it prominently in neural progenitors where it mediates Filamin A surface transport.

    Evidence Comparative siRNA knockdown of BIG1/BIG2 with transferrin recycling assay; immunohistochemistry and dominant-negative transfection in neuroblastoma cells

    PMID:16320251 PMID:16477018

    Open questions at the time
    • Whether BIG2 directly sorts TfnR or acts indirectly through membrane architecture unknown
    • FLNA transport blocked only partially by dominant-negative
  6. 2007 High

    The PKA–PP1γ regulatory circuit on BIG2 was biochemically defined: PKA phosphorylation inhibits BIG2 GEF activity, and PP1γ (not PP1α/β or PP2A) specifically reverses this inhibition, establishing a phosphorylation switch controlling ARF activation.

    Evidence In vitro PKA phosphorylation and GEP activity assay, recombinant phosphatase panel, co-immunoprecipitation of endogenous PP1γ from microsomes

    PMID:17360629

    Open questions at the time
    • Phosphorylation site(s) on BIG2 not mapped
    • In vivo relevance of the phospho-switch not demonstrated
  7. 2007 High

    BIG2 was found to control TNFR1 exosome-like vesicle release through ARF1/ARF3 and to homodimerize via DCB–HUS domain interactions, adding exosome biogenesis as a BIG2-regulated process and revealing a conserved dimerization architecture.

    Evidence siRNA knockdown with TNFR1 vesicle release assay, ARF knockdown epistasis; yeast two-hybrid and biochemical pulldown for dimerization

    PMID:17276987 PMID:17640864

    Open questions at the time
    • Functional requirement for dimerization in vesicle release untested
    • Whether BIG2 acts at MVB or earlier compartment for TNFR1 sorting unknown
  8. 2008 High

    The AKAP scaffolding role was connected to exosome secretion: BIG2 anchors RIIβ via AKAP domains B/C to mediate cAMP/PKA-dependent TNFR1 exosome-like vesicle release, while double BIG1/BIG2 knockdown revealed partially redundant roles in AP-1-dependent TGN–endosome transport of furin.

    Evidence Individual PKA regulatory subunit siRNA with TNFR1 vesicle release assay; double BIG1/BIG2 knockdown with furin retrograde transport assay

    PMID:18417613 PMID:18625701

    Open questions at the time
    • Relative contribution of BIG2 GEF versus scaffold function to exosome release unclear
    • Redundancy boundaries between BIG1 and BIG2 for different cargoes not systematically mapped
  9. 2012 High

    Upstream regulators of BIG2 TGN targeting were identified: Arl1 directly binds BIG2's N-terminus to recruit it to the trans-Golgi, and GBF1-activated ARF4/ARF5 facilitate BIG1/BIG2 TGN recruitment, establishing a GEF cascade (GBF1→ARF4/5→BIG2 recruitment→ARF1 activation).

    Evidence Liposome affinity purification for Arl1 binding; GBF1/ARF isoform-specific knockdown with BIG2 localization readouts

    PMID:22291037 PMID:23386609

    Open questions at the time
    • Whether Arl1 and ARF4/5 pathways converge or represent parallel recruitment mechanisms unknown
    • Structural basis of Arl1–BIG2 interaction not resolved
  10. 2013 High

    A GEF-independent scaffolding function was established: BIG2 anchors myosin phosphatase complexes (myosin IIA, PP1δ, MYPT1) through its C-terminal region, controlling myosin light chain phosphorylation, actin dynamics, and cell migration independently of ARF activation.

    Evidence Reciprocal co-immunoprecipitation of endogenous proteins, rescue with C-terminal domain lacking GEF activity, Transwell migration assay

    PMID:23918382

    Open questions at the time
    • Whether the myosin phosphatase scaffold and AKAP functions operate on the same or distinct BIG2 pools unknown
    • Structural basis for C-terminal myosin phosphatase binding not defined
  11. 2016 High

    BIG2 was shown to couple AKAP-scaffolded PKA to β-catenin signaling: the AKAP-C domain enables PKA-mediated β-catenin S675 phosphorylation and transcriptional co-activation, linking BIG2 vesicular trafficking to Wnt pathway output.

    Evidence Co-immunoprecipitation of BIG2 with β-catenin, AKAP domain deletion, β-catenin S675 phosphorylation assay, transcriptional reporter assay

    PMID:27162341

    Open questions at the time
    • Whether β-catenin phosphorylation occurs at a specific membrane compartment unknown
    • Contribution of PLD activity versus ARF-GTP to β-catenin signaling not fully dissected
  12. 2018 High

    In neurons, BIG2 was placed in a linear signaling axis—BIG2→ARF1→RhoA→mDia1—that polarizes dendritic Golgi outposts and supports dendrite growth, with constitutively active ARF1 rescuing BIG2-null phenotypes.

    Evidence siRNA/shRNA knockdown, constitutively active ARF1 Q71L rescue, RhoA activation assay, in utero electroporation, live-cell imaging

    PMID:29455446

    Open questions at the time
    • How BIG2 is selectively activated in dendrites versus axons unknown
    • Whether RhoA/mDia1 axis operates independently of the myosin phosphatase scaffold function unclear
  13. 2025 Medium

    Conservation of the ARF-GEF/Arf1 axis in neural stem cell polarity was demonstrated in Drosophila, where the BIG2 ortholog Sec71 with Arf1 controls myosin II cortical localization via PI(4)P, extending BIG2 function to asymmetric cell division.

    Evidence Genetic epistasis in Drosophila neuroblasts, co-immunoprecipitation of Arf1 with Sqh and Vibrator, PI(4)P localization assays

    PMID:40208939

    Open questions at the time
    • Whether mammalian BIG2 similarly controls asymmetric division in neural progenitors untested
    • Mechanism linking PI(4)P to myosin II cortical recruitment not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of BIG2 regulation (no high-resolution structure of full-length BIG2), the precise PKA phosphorylation site(s) controlling GEF activity in vivo, and how the AKAP scaffold, myosin phosphatase scaffold, and ARF-GEF functions are spatiotemporally coordinated across different membrane compartments.
  • No high-resolution structure of BIG2 or its regulatory domains
  • PKA phosphorylation sites on BIG2 not mapped
  • Spatiotemporal coordination of GEF-dependent and GEF-independent functions at different compartments unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 4
Localization
GO:0005794 Golgi apparatus 5 GO:0005768 endosome 3 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 8 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3
Partners
ARF1ARF3ARL1CTNNB1EXOC7MYH9PPP1CCPRKAR2B
Complex memberships
BIG1/BIG2 homodimerBIG2-PKA-RIIβ AKAP complexBIG2-myosin phosphatase complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 ARFGEF2 encodes BIG2, a brefeldin A-inhibited guanine nucleotide-exchange factor required for vesicle and membrane trafficking from the trans-Golgi network (TGN). Inhibition of BIG2 by BFA or dominant-negative ARFGEF2 cDNA decreases neural progenitor cell proliferation in vitro and disrupts intracellular localization of E-cadherin and beta-catenin by preventing their transport from the Golgi apparatus to the cell surface. Dominant-negative ARFGEF2 cDNA transfection, BFA inhibition, western blot, immunofluorescence in neural cell lines Nature genetics High 14647276
2002 BIG2 overexpression blocks BFA-induced redistribution of ARF1 and the AP-1 complex from membranes but not that of the COPI complex, indicating BIG2 specifically mediates AP-1 (but not COPI) membrane association through ARF activation at the TGN. BIG2 overexpression, BFA treatment, immunofluorescence for coat proteins The Journal of biological chemistry High 11777925
2002 A dominant-negative BIG2 mutant induces redistribution of AP-1 and GGA1 from membranes and causes TGN membrane tubulation, but does not affect COPI redistribution or Golgi membrane tubulation, placing BIG2 specifically in the TGN-to-endosome trafficking route via AP-1 and GGA coat proteins. Dominant-negative BIG2 mutant expression, immunofluorescence for coat proteins and organelle markers Biochemical and biophysical research communications High 12051703
2004 A population of BIG2 localizes to recycling endosomes (in addition to TGN); expression of a catalytically inactive BIG2 E738K mutant selectively induces membrane tubules from the recycling endosome compartment. BIG2 activates class I ARFs (ARF1 and ARF3) in vivo, and inactivation of either ARF exaggerates E738K-induced tubulation, indicating BIG2 maintains recycling endosome structural integrity through class I ARF activation. Catalytically inactive mutant (E738K) expression, ARF knockdown, immunofluorescence, organelle morphology analysis Molecular biology of the cell High 15385626
2003 BIG2 contains three A kinase-anchoring protein (AKAP) domains: domain A (residues 27–48) interacting with RIα and RIβ, domain B (residues 284–301) interacting with RIIα and RIIβ, and domain C (residues 517–538) interacting with RIα, RIIα, and RIIβ. BIG2 co-immunoprecipitates with endogenous RIα in HepG2 cytosol, and cAMP elevation causes BIG2 translocation from cytosol to Golgi/membrane structures. Yeast two-hybrid screen, co-immunoprecipitation of in vitro translated and endogenous proteins, deletion mutagenesis, subcellular fractionation Proceedings of the National Academy of Sciences of the United States of America High 12571360
2005 BIG2 physically interacts with exocyst protein Exo70 via its N-terminal region (amino acids 1–643). Endogenous BIG2 and Exo70 co-localize at TGN membranes and the microtubule-organizing center (MTOC)/centrosomes in HepG2 cells, suggesting functional cooperation in vesicular trafficking from TGN to plasma membrane. Yeast two-hybrid, co-immunoprecipitation of in vitro translated proteins, immunofluorescence, centrosome purification Proceedings of the National Academy of Sciences of the United States of America High 15705715
2006 BIG2, but not BIG1, associates with recycling endosomes during transferrin uptake and is required for transferrin receptor (TfnR) recycling. BIG2 siRNA knockdown increases perinuclear TfnR accumulation and slows transferrin release, while BIG1 siRNA has no effect on these processes. siRNA knockdown, immunofluorescence, density-gradient fractionation, transferrin uptake/release assay Proceedings of the National Academy of Sciences of the United States of America High 16477018
2006 BIG2 (but not BIG1) is required for AMY-1 localization to the TGN; AMY-1 co-immunoprecipitates with both BIG1 and BIG2, but RNAi knockdown demonstrates that BIG2 specifically anchors AMY-1 at the TGN. Co-immunoprecipitation with FLAG-tagged AMY-1, RNAi knockdown, immunofluorescence Genes to cells : devoted to molecular & cellular mechanisms Medium 16866877
2007 BIG2 (but not BIG1) regulates the constitutive release of full-length TNFR1 in exosome-like vesicles from human vascular endothelial cells via ARF1- and ARF3-dependent mechanisms. BIG2 co-localizes with TNFR1 in cytoplasmic vesicles and this association is disrupted by BFA. RNAi knockdown of BIG1/BIG2, TNFR1 release assay, ARF1/ARF3 knockdown, co-localization immunofluorescence, BFA treatment The Journal of biological chemistry High 17276987
2007 PKA phosphorylates BIG2 in vitro (causing electrophoretic retardation), decreasing its ARF guanine nucleotide exchange activity; protein phosphatase 1γ (PP1γ), but not PP1α, PP1β, or PP2A, restores BIG2 GEP activity after PKA phosphorylation. Endogenous PP1γ co-immunoprecipitates with BIG2 from microsomal fractions. In vitro PKA phosphorylation assay, in vitro GEP activity assay, recombinant phosphatase treatment, co-immunoprecipitation from microsomal fractions Proceedings of the National Academy of Sciences of the United States of America High 17360629
2007 BIG2 forms homodimers through interactions between DCB domains and between DCB and HUS domains within the N-terminal region, mediated by the conserved HUS box; this dimeric DCB-HUS structural unit is shared across GBF and BIG ArfGEF subfamilies and is proposed to have a regulatory role in Arf activation. Yeast two-hybrid, biochemical pulldown assays, cellular dimerization assays The Journal of biological chemistry Medium 17640864
2008 BIG2 anchors PKA regulatory subunit RIIβ via AKAP domains B and C to mediate cAMP-induced PKA-dependent release of TNFR1 exosome-like vesicles. RIIβ knockdown reduces both constitutive and cAMP-induced TNFR1 exosome-like vesicle release. siRNA knockdown of individual PKA regulatory subunits, cAMP stimulation, TNFR1 vesicle release assay, domain mapping The Journal of biological chemistry High 18625701
2008 Simultaneous RNAi knockdown of both BIG2 and BIG1 causes mislocalization of TGN/recycling endosome-associated proteins and blocks retrograde transport of furin from late endosomes to the TGN; single knockdown of either alone has less severe effects, indicating redundant roles in AP-1-dependent TGN–endosome trafficking. Double RNAi knockdown, immunofluorescence for cargo proteins, furin retrograde transport assay Molecular biology of the cell High 18417613
2009 PDE3A interacts with BIG1 and BIG2 (as components of their AKAP scaffolding complexes); selective PDE3A depletion or inhibition by cilostamide decreases membrane-associated BIG1 and BIG2 and reduces activated ARF1-GTP levels, suggesting PDE3A limits local cAMP that would otherwise drive PKA-mediated inhibition of BIG GEP activity. siRNA knockdown of PDE3A, PDE3A inhibitor (cilostamide), confocal immunofluorescence, ARF1-GTP pulldown Proceedings of the National Academy of Sciences of the United States of America Medium 19332778
2010 BIG2 is essential for early mouse embryonic development; homozygous Arfgef2 gene-trap disruption causes lethality before the 4-cell stage. Arfgef2 mRNA is maternally stored in oocytes and the embryonic gene is activated at the 4-cell stage. Gene-trap mouse line, breeding analysis, LacZ reporter expression, SNP markers for embryo genotyping The International journal of developmental biology High 20357875
2010 BIG2 depletion by siRNA specifically induces tubulation of recycling endosomes (distinct from BIG1 depletion, which fragments the Golgi), demonstrating non-redundant roles: BIG2 is specifically required for endosomal compartment integrity. siRNA knockdown, fixed and live-cell imaging, organelle marker analysis PloS one High 20360857
2012 Arl1 (an Arf-like GTPase) is necessary for Golgi recruitment of BIG2 and BIG1 to the trans-Golgi (but not for GBF1 recruitment); Arl1 binds directly to the N-terminal region of BIG2/BIG1 orthologs, directing trans-Golgi-specific ARF1 GEF activity. Liposome-based affinity purification, Arl1 knockdown in mammalian cells, immunofluorescence for BIG1/BIG2 Golgi localization The Journal of cell biology High 22291037
2012 BIG2 regulates cell migration by controlling integrin β1 recycling to the cell surface and actin remodeling. BIG2 siRNA causes perinuclear accumulation of integrin β1, increases cytosolic Arp2/3, cofilin, and vinculin levels, decreases membrane protrusions at leading edges, and impairs wound-healing migration. siRNA knockdown, DIGE proteomics, immunofluorescence, wound-healing assay, integrin β1 surface trafficking assay Proceedings of the National Academy of Sciences of the United States of America High 22908276
2013 GBF1-activated ARF4 and ARF5 (but not ARF3) facilitate BIG1 and BIG2 recruitment to the TGN, establishing a functional GEF cascade where GBF1 acts upstream of BIG1/BIG2 in the Golgi/TGN system. GBF1 depletion, dominant-negative GBF1, ARF isoform-specific knockdown, immunofluorescence for BIG1/BIG2 localization, ultrastructural localization of GBF1 The Journal of biological chemistry High 23386609
2013 BIG1 and BIG2 anchor myosin phosphatase complexes (comprising myosin IIA, protein phosphatase 1δ, and myosin phosphatase-targeting subunit 1) independently of their ARF-GEF catalytic activity. Depletion of BIG1 or BIG2 enhances myosin regulatory light chain phosphorylation (T18/S19) and F-actin content, impairing cell migration; these effects are rescued by overexpression of the BIG C-terminal sequence lacking GEF activity. Reciprocal co-immunoprecipitation of endogenous proteins, siRNA depletion, rescue with C-terminal domain overexpression, myosin light chain phosphorylation assay, Transwell migration assay Proceedings of the National Academy of Sciences of the United States of America High 23918382
2016 BIG2 co-immunoprecipitates with β-catenin; BIG2 depletion or expression of GEF-inactive mutant causes β-catenin accumulation at perinuclear Golgi structures. BIG2 AKAP-C domain is required for PKA-mediated phosphorylation of β-catenin at S675 and for β-catenin transcription coactivator function, requiring both phospholipase D activity and vesicular trafficking. Co-immunoprecipitation, siRNA depletion, GEF-inactive mutant overexpression, β-catenin S675 phosphorylation assay, transcriptional reporter assay, AKAP domain deletion Proceedings of the National Academy of Sciences of the United States of America High 27162341
2018 BIG2 activates ARF1 in hippocampal neurons to promote dendritic Golgi polarization and dendrite growth and maintenance through a BIG2→ARF1→RhoA→mDia1 signaling axis. Constitutively active ARF1 Q71L rescues BIG2-null dendritic morphogenesis defects, and BIG2+ARF1 co-overexpression activates RhoA; mDia1 was identified as the downstream effector. siRNA/shRNA knockdown, constitutively active ARF1 rescue, RhoA activation assay, co-localization immunofluorescence, in utero electroporation, live-cell imaging of dendritic Golgi Molecular neurobiology High 29455446
2006 BIG2 protein is most strongly expressed in neural progenitors along the neuroependymal lining of the ventricular zone during development; dominant-negative ARFGEF2 transfection in neuroblastoma cells partially blocks FLNA transport from the Golgi apparatus to the cell membrane, suggesting BIG2 mediates targeted transport of Filamin A to the cell surface in neural progenitors. Immunohistochemistry, in situ hybridization, western blot, dominant-negative transfection with immunofluorescence for FLNA localization The Journal of comparative neurology Medium 16320251
2025 The Drosophila ARFGEF2 ortholog Sec71 (together with Arf1) controls asymmetric division of neural stem cells by facilitating localization of myosin II regulatory light chain (Sqh) to the NSC cortex, dependent on PI(4)P production. Arf1 physically associates with Sqh and the PITP Vibrator, and Arf1/Sec71 facilitate PI(4)P localization to the neuroblast cortex. Genetic epistasis in Drosophila, co-immunoprecipitation of Arf1 with Sqh and Vibrator, PI(4)P localization by immunofluorescence, neuroblast polarity assays Proceedings of the National Academy of Sciences of the United States of America Medium 40208939

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. Nature genetics 287 14647276
1995 Overlapping and differential expression of BIG-2, BIG-1, TAG-1, and F3: four members of an axon-associated cell adhesion molecule subgroup of the immunoglobulin superfamily. Journal of neurobiology 141 8586965
2008 BIG-2 mediates olfactory axon convergence to target glomeruli. Neuron 130 18367085
2004 BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: its localization to recycling endosomes and implication in the endosome integrity. Molecular biology of the cell 121 15385626
2002 Overexpression of an ADP-ribosylation factor-guanine nucleotide exchange factor, BIG2, uncouples brefeldin A-induced adaptor protein-1 coat dissociation and membrane tubulation. The Journal of biological chemistry 93 11777925
2003 Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2). Proceedings of the National Academy of Sciences of the United States of America 80 12571360
2008 Redundant roles of BIG2 and BIG1, guanine-nucleotide exchange factors for ADP-ribosylation factors in membrane traffic between the trans-Golgi network and endosomes. Molecular biology of the cell 75 18417613
2002 Dominant-negative mutant of BIG2, an ARF-guanine nucleotide exchange factor, specifically affects membrane trafficking from the trans-Golgi network through inhibiting membrane association of AP-1 and GGA coat proteins. Biochemical and biophysical research communications 68 12051703
2013 The Sec7 guanine nucleotide exchange factor GBF1 regulates membrane recruitment of BIG1 and BIG2 guanine nucleotide exchange factors to the trans-Golgi network (TGN). The Journal of biological chemistry 66 23386609
2012 The small G protein Arl1 directs the trans-Golgi-specific targeting of the Arf1 exchange factors BIG1 and BIG2. The Journal of cell biology 57 22291037
2007 The brefeldin A-inhibited guanine nucleotide-exchange protein, BIG2, regulates the constitutive release of TNFR1 exosome-like vesicles. The Journal of biological chemistry 56 17276987
2006 Association of brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2) with recycling endosomes during transferrin uptake. Proceedings of the National Academy of Sciences of the United States of America 53 16477018
2005 Interaction of BIG2, a brefeldin A-inhibited guanine nucleotide-exchange protein, with exocyst protein Exo70. Proceedings of the National Academy of Sciences of the United States of America 45 15705715
2007 Regulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) and BIG2 activity via PKA and protein phosphatase 1gamma. Proceedings of the National Academy of Sciences of the United States of America 44 17360629
2007 Interactions between conserved domains within homodimers in the BIG1, BIG2, and GBF1 Arf guanine nucleotide exchange factors. The Journal of biological chemistry 43 17640864
2006 Overlapping expression of ARFGEF2 and Filamin A in the neuroependymal lining of the lateral ventricles: insights into the cause of periventricular heterotopia. The Journal of comparative neurology 37 16320251
2010 Specific functions of BIG1 and BIG2 in endomembrane organization. PloS one 36 20360857
2009 Movement disorder and neuronal migration disorder due to ARFGEF2 mutation. Neurogenetics 30 19384555
2017 BEN3/BIG2 ARF GEF is Involved in Brefeldin A-Sensitive Trafficking at the trans-Golgi Network/Early Endosome in Arabidopsis thaliana. Plant & cell physiology 27 29016942
2008 cAMP-dependent protein kinase A (PKA) signaling induces TNFR1 exosome-like vesicle release via anchoring of PKA regulatory subunit RIIbeta to BIG2. The Journal of biological chemistry 26 18625701
2013 Arf guanine nucleotide-exchange factors BIG1 and BIG2 regulate nonmuscle myosin IIA activity by anchoring myosin phosphatase complex. Proceedings of the National Academy of Sciences of the United States of America 25 23918382
2006 AMY-1 (associate of Myc-1) localization to the trans-Golgi network through interacting with BIG2, a guanine-nucleotide exchange factor for ADP-ribosylation factors. Genes to cells : devoted to molecular & cellular mechanisms 25 16866877
2009 Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity. Proceedings of the National Academy of Sciences of the United States of America 23 19332778
2018 BIG2-ARF1-RhoA-mDia1 Signaling Regulates Dendritic Golgi Polarization in Hippocampal Neurons. Molecular neurobiology 22 29455446
2013 West syndrome, microcephaly, grey matter heterotopia and hypoplasia of corpus callosum due to a novel ARFGEF2 mutation. Journal of medical genetics 22 23812912
2005 Expression of BIG2 and analysis of its function in mammalian cells. Methods in enzymology 20 16413271
2003 Cloning and characterization of the human neural cell adhesion molecule, CNTN4 (alias BIG-2). Cytogenetic and genome research 20 14571131
2016 Enhancement of β-catenin activity by BIG1 plus BIG2 via Arf activation and cAMP signals. Proceedings of the National Academy of Sciences of the United States of America 19 27162341
2015 The expanding phenotypic spectrum of ARFGEF2 gene mutation: Cardiomyopathy and movement disorder. Brain & development 19 26126837
2014 Periventricular nodular heterotopia and dystonia due to an ARFGEF2 mutation. Pediatric neurology 17 25160555
2010 Early embryonic lethality in gene trap mice with disruption of the Arfgef2 gene. The International journal of developmental biology 17 20857375
2014 Filamin A mediated Big2 dependent endocytosis: From apical abscission to periventricular heterotopia. Tissue barriers 16 25097827
2012 Brefeldin A-inhibited ADP-ribosylation factor activator BIG2 regulates cell migration via integrin β1 cycling and actin remodeling. Proceedings of the National Academy of Sciences of the United States of America 14 22908276
2005 BIG1 and BIG2, brefeldin A-inhibited guanine nucleotide-exchange factors for ADP-ribosylation factors. Methods in enzymology 14 16413268
2013 Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: case study and literature review. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 11 23755938
1997 A novel splice variant of the cell adhesion molecule BIG-2 is expressed in the olfactory and vomeronasal neuroepithelia. Brain research. Molecular brain research 11 9221934
2019 Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 31199673
2014 Filamin A and Big2: a shared endocytic pathway. Bioarchitecture 9 24709996
2011 Nanomechanics of Ig-like domains of human contactin (BIG-2). Journal of molecular modeling 6 21445711
2025 Arf1 and ARFGEF2/Sec71 control neuroblast polarity by anchoring nonmuscle myosin II. Proceedings of the National Academy of Sciences of the United States of America 1 40208939