Affinage

ARHGEF2

Rho guanine nucleotide exchange factor 2 · UniProt Q92974

Length
986 aa
Mass
111.5 kDa
Annotated
2026-06-14
100 papers in source corpus 64 papers cited in narrative 64 extracted findings
Cross-family judge vs UniProt: Affinage preferred

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARHGEF2 (GEF-H1/Lfc) is a Dbl-family guanine nucleotide exchange factor that catalytically and specifically activates RhoA (and to a lesser extent Rac1) to drive actin stress fiber formation, cell contractility, mitotic spindle assembly, epithelial barrier regulation, and innate immune signaling (PMID:8910315, PMID:9857026, PMID:9890991). Its activity is gated by microtubule binding through its C-terminal coiled-coil region: microtubule-associated GEF-H1 is held in an autoinhibited state, and microtubule depolymerization or release from the cytoskeleton liberates active GEF-H1 to load GTP onto RhoA (PMID:11912491, PMID:18287519, PMID:31420453). Release is achieved by diverse inputs — drug-induced or mechanically/matrix-stiffness-induced microtubule destabilization (PMID:18287519, PMID:22593214), displacement by Gα subunits and RalA–Sec5 exocyst coupling downstream of GPCR ligands (PMID:25209408, PMID:22898781), and bacterial effectors (EPEC EspG/Orf3, Vibrio VopO, Bartonella BepC) that destabilize microtubules or directly bind and relocalize GEF-H1 to activate RhoA-ROCK signaling (PMID:15318166, PMID:25738744, PMID:33508040). A dense phosphoregulatory network tunes the protein: phosphorylation by PAK1, PAK4, PAR1b/MARK2, MARK3, PKA/PKG creates 14-3-3 binding sites that tether GEF-H1 to microtubules and suppress exchange activity, while ERK (Thr678), NEK9, and HUNK (Ser645) phosphorylation enhance activity; PP2A reverses inhibitory phosphorylation at Ser885/Ser151 to restore activity (PMID:14970201, PMID:15827085, PMID:22072711, PMID:29089450, PMID:18211802, PMID:33500736, PMID:37193711, PMID:33762326, PMID:25209408). GEF-H1 is sequestered at tight junctions by cingulin and paracingulin to restrain epithelial RhoA and G1/S progression (PMID:15866167, PMID:18653465), and is essential for RhoA-dependent mitotic spindle assembly and cleavage-furrow Rho activation during cytokinesis (PMID:15976019, PMID:17488622). Beyond its catalytic role, GEF-H1 acts as a non-catalytic adaptor linking PP2A to the scaffold KSR-1 to activate MAPK downstream of oncogenic RAS (PMID:24525234), and is required for innate immune signaling through NOD1/NOD2–RIP2 to NF-κB, RIG-I/Mda5 to IRF3/IFN-β, and an IKKε–IRF5 peptidoglycan-sensing pathway (PMID:19043560, PMID:21887730, PMID:24270516, PMID:30902986). Homozygous frameshift mutation in ARHGEF2 causes intellectual disability and midbrain-hindbrain malformation, with loss shifting mitotic spindle orientation toward symmetric divisions and reducing RhoA/ROCK/MLC signaling (PMID:28453519).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Established that ARHGEF2 is a catalytically active, substrate-selective exchange factor, defining its core biochemical identity.

    Evidence In vitro GDP dissociation and GTPγS exchange assays with RhoA, Rac, Cdc42, and Ras

    PMID:8910315 PMID:9857026

    Open questions at the time
    • Cellular triggers of exchange activity not yet defined
    • Relative physiological weight of RhoA vs Rac activity unresolved
  2. 1999 High

    Linked GEF activity to a cytoskeletal localization, showing GEF-H1 acts on RhoA/Rac to remodel actin and signal to JNK.

    Evidence Immunofluorescence localization, dominant-negative GTPase epistasis, and JNK assays in NIH 3T3 cells

    PMID:7629163 PMID:9890991

    Open questions at the time
    • Mechanism coupling microtubule localization to activity state not established
    • Domain basis of autoinhibition unknown
  3. 2002 High

    Defined the central regulatory logic: microtubule-bound GEF-H1 is inactive and microtubule depolymerization activates RhoA, resolving how cytoskeletal state controls exchange activity.

    Evidence Microtubule-binding mutants, nocodazole treatment, and dominant-negative epistasis with morphology readouts

    PMID:11912491

    Open questions at the time
    • Molecular nature of the autoinhibited conformation not defined
    • How depolymerization is sensed and transmitted unclear
  4. 2005 High

    Revealed phosphorylation-coupled 14-3-3 binding as the molecular switch tethering GEF-H1 to microtubules, and PAK4 as a writer producing alternative (lamellipodial) outputs.

    Evidence In vitro kinase assays (PAK1 Ser885, PAK4 Ser810), site mutagenesis, and 14-3-3 Co-IP

    PMID:14970201 PMID:15827085

    Open questions at the time
    • Erasers restoring active state not yet identified
    • Stoichiometry and combinatorial logic of multisite phosphorylation unknown
  5. 2005 High

    Demonstrated regulated sequestration by binding partners (cingulin, neurabin/spinophilin) couples GEF-H1-RhoA to tight-junction and synaptic morphology, extending its role beyond microtubules.

    Evidence Direct binding, Co-IP, RNAi, and morphology/cell cycle readouts in MDCK cells and neurons

    PMID:15866167 PMID:15996550

    Open questions at the time
    • Whether junction and microtubule pools are exchangeable not resolved
    • Quantitative contribution of each sequestering partner unclear
  6. 2007 High

    Placed GEF-H1 in cell-cycle control, showing mitotic kinases inhibit it and timed dephosphorylation enables furrow RhoA activation distinct from Ect2.

    Evidence In vitro Aurora A/B and Cdk1/CyclinB kinase assays, FRET RhoA biosensor, and siRNA in mitotic cells

    PMID:15976019 PMID:17488622

    Open questions at the time
    • Phosphatase timing the mitotic-exit activation not pinned down
    • Spatial coordination with Ect2 not fully mapped
  7. 2008 High

    Established GEF-H1 as the necessary and sufficient transducer of microtubule depolymerization into RhoA-ROCK-MLC contractility, and identified ERK (Thr678) as an activating writer.

    Evidence siRNA with rescue, RhoA/ROCK/MLC readouts, and in vitro ERK phosphorylation with mutagenesis

    PMID:18211802 PMID:18287519

    Open questions at the time
    • How activating versus inhibitory phosphorylation are integrated unclear
    • Upstream signals selecting ERK input not defined
  8. 2009 High

    Expanded GEF-H1 into innate immunity, GPCR-linked transcription, and inhibitory adaptors, showing it transduces pathogen and receptor signals to RhoA/RhoB and gene expression.

    Evidence NOD1 Co-IP/NF-κB reporter, TRIF-dependent RhoB activation in DCs, ZONAB/cyclin D1 reporter, Tctex-1/AKAP121-PKA, paracingulin binding

    PMID:16917499 PMID:18653465 PMID:19043560 PMID:19208802 PMID:19667072 PMID:19730435 PMID:20463241

    Open questions at the time
    • GTPase selectivity (RhoA vs RhoB vs Rac) per stimulus not mechanistically explained
    • How the same GEF reaches distinct downstream programs unresolved
  9. 2011 High

    Showed mechanical force and additional kinases/partners (PAR1b/MARK2, CAPN6) reroute GEF-H1 output between RhoA and Rac, linking it to mechanotransduction and adhesion reinforcement.

    Evidence Magnetic bead force with GEF assays, in vitro MARK2 kinase assays, and CAPN6 Co-IP/siRNA with Rac1 activation

    PMID:21406564 PMID:21513698 PMID:21572419 PMID:21887730 PMID:22002306 PMID:22072711

    Open questions at the time
    • Determinants of RhoA-versus-Rac choice at adhesions unclear
    • Integration of force and phosphorylation inputs not quantitatively modeled
  10. 2012 Medium

    Identified non-microtubule scaffolds (Sec5/RalA exocyst, ASAP1, FAM123A, CAMSAP3) that localize and gate GEF-H1, broadening its role into exocytosis and non-centrosomal microtubule control.

    Evidence Direct binding/Co-IP, RalA-dependency tests, siRNA with RhoA/Rac activity and exocytosis/podosome readouts

    PMID:21352810 PMID:22898781 PMID:22949735 PMID:23432781

    Open questions at the time
    • Several interactions rest on single-lab Co-IP/MS without reciprocal in vivo validation
    • Hierarchy among competing sequestering partners unknown
  11. 2013 High

    Defined GEF-H1 as a master antiviral sensor and showed a single GEF can sequentially activate Rac then RhoA via distinct phosphosites in cytokine signaling.

    Evidence Arhgef2 knockout mice with viral challenge and IRF3/IFN-β readouts; phosphosite-mutant Rac/RhoA activation assays for TNF-α

    PMID:23389627 PMID:24270516

    Open questions at the time
    • Molecular basis distinguishing Rac- versus RhoA-directed conformations unresolved
    • How microtubule release links to RNA sensing mechanistically unclear
  12. 2014 High

    Uncovered a catalysis-independent adaptor function (PP2A–KSR-1–MAPK) and defined a MARK3/LKB1–PP2A writer-eraser pair at Ser151, plus GPCR-driven activation via Gα/Gβγ displacement of Tctex-1.

    Evidence Co-IP of ternary complexes, GEF-catalytic-dead mutants, in vitro MARK3 kinase assay, and direct G-protein binding with phosphatase assays

    PMID:24525234 PMID:24681784 PMID:25209408 PMID:26759237 PMID:29089450

    Open questions at the time
    • Structural basis of the adaptor versus catalytic modes not resolved
    • How PP2A is targeted to specific GEF-H1 sites unclear
  13. 2016 High

    Showed protein turnover (autophagy/p62) and stiffness/channel signaling (TRPC3-Nox2) regulate GEF-H1 abundance and activity, controlling migration mode and fibrotic responses.

    Evidence Autophagy-deficient knockouts with p62 Co-IP, TRPC3 interactomics/inhibition, and JAM-A tension experiments

    PMID:26985018 PMID:27120804 PMID:27991560 PMID:33762326

    Open questions at the time
    • Signals selecting degradation versus phosphoregulation unknown
    • TRPC3-Nox2 mechanism rests on single-lab pharmacology
  14. 2019 High

    Provided spatiotemporal resolution of activation and extended innate roles, mapping autoinhibited microtubule pool versus cortically activated pools and IKKε–IRF5 and DC cross-presentation functions.

    Evidence GEF-H1 FRET biosensor with live MT imaging, Src inhibition, and Arhgef2 knockout immune/infection models

    PMID:30902986 PMID:31420453 PMID:31553907

    Open questions at the time
    • Structural autoinhibition mechanism still not solved at atomic level
    • How peripheral activation bands are spatially restricted unclear
  15. 2021 High

    Connected disease-relevant transcriptional, translational, and kinase inputs (NEK9, HUNK, KRAS promoter control, m6A/YTHDF1) to GEF-H1-RhoA in cancer and metabolic stress.

    Evidence In vitro kinase assays (NEK9, HUNK Ser645), m6A-MeRIP/RIP-seq with knockout mouse, KRAS promoter dissection, and macropinocytosis assays

    PMID:25738744 PMID:26152517 PMID:27835861 PMID:32692911 PMID:32789168 PMID:33500736 PMID:33508040 PMID:33653692 PMID:34968454 PMID:37193711

    Open questions at the time
    • Integration of transcriptional, translational, and post-translational control into one quantitative model lacking
    • Tissue-specific dominance of each regulatory axis unresolved
  16. 2022 Medium

    Validated GEF-H1's autoregulatory C-terminus as a druggable target, blocking RhoA binding to suppress fibrosis, barrier disruption, and vascular leakage in vivo.

    Evidence In silico-designed peptide inhibitors with in vitro binding and in vivo retinal disease model

    PMID:35681428

    Open questions at the time
    • Tool-compound specificity and pharmacokinetics not fully characterized
    • Selectivity over other RhoGEFs not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and quantitative model explaining how a single GEF integrates microtubule state, dozens of phosphorylation events, competing sequestering partners, and adaptor functions to select between RhoA, Rac, RhoB, and non-catalytic outputs remains to be built.
  • No atomic structure of full-length autoinhibited or activated GEF-H1
  • Rules governing GTPase-output selection per stimulus undefined
  • Hierarchy and crosstalk among regulatory inputs unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005856 cytoskeleton 3 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
14-3-3CINGULINNOD1RAC1RHOARIP2SEC5TCTEX-1/DYNLT1
Complex memberships
AMPA receptor complexNOD2-RIP2 signaling complexPP2A-KSR-1 adaptor complexexocyst (via Sec5)

Evidence

Reading pass · 64 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Lfc (ARHGEF2) was identified as an oncoprotein containing a Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain; deletion analysis showed both PH and DH domains are required for NIH 3T3 transformation, with the PH domain mediating membrane recruitment necessary for transforming activity. Retroviral cDNA transfer, NIH 3T3 transformation assay, NH2- and COOH-terminal deletion analysis, isoprenylation site replacement The Journal of biological chemistry High 7629163
1996 Lfc (ARHGEF2) functions as a highly specific guanine nucleotide exchange factor for RhoA in vitro, catalytically stimulating >10-fold GDP dissociation from RhoA; it forms tight complexes with nucleotide-depleted RhoA and, uniquely, also binds Rac (but not Cdc42 or Ras), distinguishing it from other Dbl-family GEFs. In vitro [3H]GDP dissociation assay, GDP-[35S]GTPγS exchange assay, biochemical pulldown/complex formation The Journal of biological chemistry High 8910315
1998 GEF-H1 (ARHGEF2) stimulates guanine nucleotide exchange on Rac and Rho but not Cdc42, TC10, or Ras; it colocalizes with microtubules through its carboxyl-terminal coiled-coil domain, and overexpression in COS-7 cells induces membrane ruffles. In vitro GEF assay, immunofluorescence colocalization, domain analysis, COS-7 overexpression The Journal of biological chemistry High 9857026
1999 Lfc (ARHGEF2) localizes to microtubules via its PH domain interaction with tubulin; overexpression in NIH 3T3 cells induces actin stress fibers and membrane ruffles consistent with RhoA and Rac1 activation, and Lfc stimulates JNK activity in a Rac1-dependent (and partially RhoA-dependent) manner. Immunofluorescence localization, dominant-negative GTPase epistasis, JNK activity assay, GTP-bound Rac measurement The Journal of biological chemistry High 9890991
2002 GEF-H1 (ARHGEF2) is regulated by microtubule binding: GEF-H1 mutants deficient in microtubule binding have higher RhoA GEF activity, and drug-induced microtubule depolymerization phenocopies active GEF-H1 expression in a dominant-negative GEF-H1-inhibitable manner, establishing that microtubule-bound GEF-H1 is in an inactive state. Microtubule-binding mutant analysis, nocodazole treatment, dominant-negative GEF-H1 expression, morphology/actin organization assay, gene expression analysis Nature cell biology High 11912491
2004 PAK1 phosphorylates GEF-H1 at Ser885 (within the carboxyl-terminal inhibitory region), inducing 14-3-3 binding to GEF-H1 and relocation of 14-3-3 to microtubules; the carboxyl-terminal coiled-coil region of GEF-H1 is required for microtubule-dependent suppression of its GEF activity. Affinity-based kinase screen, in vitro phosphorylation assay, site-directed mutagenesis, Co-IP/pulldown for 14-3-3 binding, immunofluorescence The Journal of biological chemistry High 14970201
2004 EPEC effectors EspG and Orf3 interact with tubulin and destabilize microtubules in vitro, thereby releasing GEF-H1 and activating RhoA-ROCK signaling to induce actin stress fibers; dominant-negative GEF-H1 and dominant-negative RhoA (but not Rac1/Cdc42) block EspG/Orf3-induced stress fiber formation. In vitro microtubule destabilization assay, dominant-negative epistasis, ROCK inhibitor treatment, bacterial infection assay The EMBO journal High 15318166
2005 PAK4 directly associates with GEF-H1 through a novel GEF-H1 interaction domain (GID) in PAK4 and phosphorylates GEF-H1 at Ser810, blocking stress fiber formation while promoting lamellipodia; the endogenous PAK4–GEF-H1 complex associates with microtubules, and PAK4 phosphorylation releases GEF-H1 into the cytoplasm. Co-IP, in vitro phosphorylation, domain mapping, siRNA knockdown, immunofluorescence in NIH-3T3 cells Journal of cell science High 15827085
2005 GEF-H1 (Lfc/ARHGEF2) directly interacts with cingulin (a tight-junction adaptor protein); cingulin binding inhibits GEF-H1 RhoA GEF activity, providing a mechanism by which tight junction formation downregulates RhoA and inhibits G1/S cell cycle progression. Direct binding assay, RNAi knockdown, RhoA activation assay, G1/S phase transition assay in MDCK cells Developmental cell High 15866167
2005 Lfc (ARHGEF2) interacts with neurabin and spinophilin via its coiled-coil domain; upon neuronal stimulation, Lfc translocates from dendritic shafts (where it associates with microtubules) to spines, reducing spine length and size through RhoA in a coiled-coil-dependent manner. Yeast two-hybrid, Co-IP, immunofluorescence/live imaging in neurons, domain deletion analysis Neuron High 15996550
2005 Lfc (ARHGEF2) is required for mitotic spindle assembly during prophase/prometaphase; inhibition of Lfc causes spindle defects and mitotic delay, rescued by constitutively active RhoA, placing Lfc upstream of RhoA in a pathway involving mDia1 for spindle formation. Antibody microinjection/dominant-negative, RhoA rescue epistasis, live-cell microscopy, cell cycle analysis Proceedings of the National Academy of Sciences of the United States of America High 15976019
2006 Mutant p53 proteins (V157F, R175H, R248Q) transcriptionally activate GEF-H1 expression, leading to RhoA activation and accelerated tumor cell proliferation; growth of mutant p53 cells depends on GEF-H1 expression whereas wild-type p53 cells do not. Inducible mutant p53 cell lines, expression profiling, RhoA activation assay, siRNA knockdown, cell growth assay Cancer research Medium 16778209
2006 TRIF-dependent (but not MyD88-dependent) LPS signaling in dendritic cells activates GEF-H1, which in turn activates RhoB (but not RhoA, Rac, or Cdc42); GEF-H1–RhoB drives surface MHCII expression required for CD4+ T cell activation. RNAi knockdown, dominant-negative constructs, Rho activation assays (pull-down), immunofluorescence colocalization, MyD88/TRIF knockout DCs The EMBO journal High 16917499
2007 GEF-H1 localizes to the mitotic apparatus (cortical microtubule tips and midbody); Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, inhibiting its catalytic activity during mitosis; dephosphorylation before cytokinesis allows GEF-H1-dependent RhoA GTP-loading at the cleavage furrow, distinct from Ect2-dependent Rho activation. Immunofluorescence localization, in vitro kinase assay (Aurora A/B, Cdk1/Cyclin B), live-cell RhoA biosensor (FRET), siRNA knockdown, GEF-H1 catalytic activity assay Developmental cell High 17488622
2008 GEF-H1 is required and sufficient to mediate nocodazole-induced RhoA activation and cell contractility; siRNA depletion of GEF-H1 prevents nocodazole-induced RhoA activation, ROCK activation, MLC phosphorylation, and cell contraction, rescued by siRNA-resistant GEF-H1 re-expression. siRNA knockdown, rescue with siRNA-resistant GEF-H1, RhoA and ROCK activity assays, MLC phosphorylation western blot, nocodazole treatment Molecular biology of the cell High 18287519
2008 ERK1/2 phosphorylate GEF-H1 at Thr678, enhancing its guanine nucleotide exchange activity toward RhoA; ERK pathway inhibition (PD184352) abolishes this phosphorylation. In vitro ERK1/2 phosphorylation assay, site-directed mutagenesis (Thr678), GEF activity assay, pharmacological ERK inhibition Biochemical and biophysical research communications High 18211802
2008 GEF-H1 interacts with NOD1 and is required for RIP2-dependent NF-κB activation in response to Shigella effectors IpgB2 and OspB and the NOD1 ligand γTriDAP; GEF-H1 is also required for Shigella cell invasion via RhoA activation. Co-IP (GEF-H1–NOD1 interaction), siRNA knockdown, NF-κB reporter assay, bacterial invasion assay PLoS pathogens High 19043560
2009 Lfc (ARHGEF2) localizes to the Golgi apparatus and growth cones in developing neurons and negatively regulates neurite sprouting and axon formation via RhoA; Tctex-1 (dynein light chain) physically interacts with Lfc, inhibiting its GEF activity, decreasing Rho-GTP, and antagonizing Lfc during neurite formation. Immunofluorescence, Co-IP (Lfc–Tctex-1), RhoA activity assay, siRNA knockdown, axon formation assay The Journal of neuroscience High 20463241
2009 Lfc (ARHGEF2) and its negative regulator Tctex-1 determine the balance between proliferative symmetric and neurogenic asymmetric divisions of cortical radial precursors; Lfc knockdown maintains cells as cycling radial precursors while Tctex-1 knockdown promotes neurogenesis; the two proteins regulate mitotic spindle orientation. Morpholino/siRNA knockdown in cortical precursors in vitro and in vivo, lineage tracing, spindle orientation analysis Nature neuroscience High 19448628
2009 PKA phosphorylates Lfc (ARHGEF2) in an AKAP121-dependent manner; this phosphorylation promotes 14-3-3 binding to Lfc in a phosphorylation-dependent manner and suppresses Lfc exchange activity on RhoA; Tctex-1 competes with 14-3-3 for Lfc binding. Co-IP (Lfc–AKAP121, Lfc–14-3-3), in vitro PKA phosphorylation, forskolin treatment, RhoA GEF activity assay, 14-3-3 binding mutant analysis Molecular and cellular biology High 19667072
2009 GEF-H1 directly interacts with paracingulin (at epithelial junctions), and paracingulin depletion increases RhoA activity; paracingulin is required for efficient recruitment of GEF-H1 to junctions, linking junction assembly to RhoA regulation. In vitro binding assay, Co-IP, siRNA knockdown, RhoA activation pull-down, immunofluorescence Molecular biology of the cell High 18653465
2009 GEF-H1 interacts with the Y-box transcription factor ZONAB/DbpA; GEF-H1 overexpression induces nuclear ZONAB accumulation and activates ZONAB-dependent transcription; GEF-H1 and ZONAB together are required for RhoA-dependent cyclin D1 expression. Co-IP (GEF-H1–ZONAB), overexpression, cyclin D1 promoter reporter, siRNA knockdown, immunofluorescence EMBO reports Medium 19730435
2009 GEF-H1 is a component of the AMPA receptor complex in the brain; it is enriched in the postsynaptic density, colocalizes with GluR1 at spines, and negatively regulates spine density and length through RhoA; AMPA-R-dependent changes in spine morphology are abolished by GEF-H1 knockdown. Co-IP from brain lysate, immunofluorescence, siRNA knockdown, spine morphology analysis, RhoA activity assay Proceedings of the National Academy of Sciences of the United States of America High 19208802
2009 TNF-α activates GEF-H1 via ERK-mediated phosphorylation of Thr678 in tubular epithelial cells, leading to RhoA activation, MLC phosphorylation, and increased paracellular permeability; GEF-H1 was identified as a TNF-α-activated RhoGEF using a RhoG17A affinity precipitation/mass spectrometry approach. RhoG17A affinity precipitation/mass spectrometry, siRNA knockdown, MEK inhibitor, phospho-specific western blot, permeability assay The Journal of biological chemistry High 19261619
2010 TGF-β transcriptionally upregulates GEF-H1 in a Smad4-dependent manner in RPE cells; GEF-H1 induction leads to RhoA activation and is required for TGF-β-induced α-SMA expression and cell migration. Genome-wide expression analysis, Smad4-dependent transcription assay, GEF-H1 siRNA knockdown, RhoA activity assay, cell migration assay Molecular biology of the cell High 20089843
2010 Lfc (ARHGEF2) and p114-RhoGEF mediate Wnt-3a/Dishevelled-induced RhoA activation and neurite retraction; Lfc and p114-RhoGEF physically bind Dvl and Daam1, and their knockdown suppresses Dvl- and Wnt-3a-induced RhoA activation and neurite retraction. shRNA screen, Co-IP (Lfc–Dvl, Lfc–Daam1), RhoA activation assay, neurite retraction assay in N1E-115 cells Molecular biology of the cell High 20810787
2011 Mechanical force on integrins triggers GEF-H1 catalytic activation via ERK downstream of a FAK–Ras signaling cascade, and recruits GEF-H1 to adhesion complexes; this is distinct from LARG activation (which occurs via Fyn), and both GEFs are required for force-induced cellular stiffening (reinforcement). Magnetic bead force application, biochemical fractionation, GEF activity assay, siRNA knockdown, traction force microscopy Nature cell biology High 21572419
2011 GEF-H1 is required for NOD2- and RIP2-dependent NF-κB activation; GEF-H1 functions downstream of NOD2 as part of RIP2-containing signaling complexes and mediates Src tyrosine kinase-dependent phosphorylation of RIP2; the 3020insC NOD2 variant associated with Crohn's disease fails to activate this GEF-H1-dependent pathway. siRNA knockdown, Co-IP (GEF-H1–RIP2–NOD2), NF-κB reporter assay, confocal microscopy, macrophage activation assay Inflammatory bowel diseases High 21887730
2011 PAR1b/MARK2 phosphorylates GEF-H1 at Ser885 and Ser959, inhibiting GEF-H1 RhoA-specific GEF activity and suppressing stress fiber formation; Par1b-phosphorylated GEF-H1 loses the ability to activate RhoA. In vitro kinase assay, phosphorylation site mutagenesis, RhoA GEF activity assay, stress fiber formation assay The Journal of biological chemistry High 22072711
2011 Par1b/MARK2 phosphorylates GEF-H1 at multiple conserved serine residues, releasing GEF-H1 from microtubules and abrogating GEF-H1-induced microtubule stabilization/acetylation; non-phosphorylatable GEF-H1 (3SA mutant) remains statically bound to microtubules as visualized by live-cell imaging. In vitro kinase assay, immunofluorescence, live-cell time-lapse imaging of GFP-GEF-H1, microtubule acetylation assay Biochemical and biophysical research communications High 21513698
2011 Calpain-6 (CAPN6) co-localizes and physically interacts with GEF-H1 on microtubules; CAPN6 knockdown causes GEF-H1 to translocate from microtubules to the lamellipodial region and interact with Rac1, leading to Rac1 activation, increased cell migration, and lamellipodial protrusion; this Rac1 activation requires GEF-H1. siRNA knockdown, Co-IP (CAPN6–GEF-H1), immunofluorescence, Rac1 and RhoA activity assays, migration assay Journal of cell science High 21406564
2012 GEF-H1 directly binds exocyst component Sec5 in a RalA GTPase-dependent manner; this interaction promotes RhoA activation, regulates exocyst assembly/localization, and is required for exocytosis. Direct binding assay (pulldown), Co-IP (GEF-H1–Sec5, RalA-dependence), RhoA activation assay, exocytosis assay, siRNA knockdown Developmental cell High 22898781
2012 Non-centrosomal microtubules anchored by CAMSAP3 (Nezha) preferentially sequester GEF-H1; CAMSAP3 depletion increases the soluble pool of GEF-H1, upregulates RhoA activity, and promotes actin stress fiber formation; detyrosinated microtubules do not efficiently interact with GEF-H1. siRNA knockdown, RhoA activity assay, immunofluorescence, subcellular fractionation Genes to cells Medium 23432781
2012 GEFH1 binds the BAR domain of ASAP1 (validated by endogenous Co-IP) and colocalizes with ASAP1 in podosomes; GEFH1 overexpression inhibits podosome assembly and ASAP1 GAP activity, while GEFH1 knockdown increases podosome assembly rate. Yeast two-hybrid, endogenous Co-IP, siRNA knockdown, overexpression, podosome assembly assay Biochemical and biophysical research communications Medium 21352810
2012 Microtubule stability is diminished by a stiff 3D extracellular matrix, leading to activation of GEF-H1 and RhoA; GEF-H1 loss decreases cell contraction and invasion through 3D matrices; MEK/ERK pathway does not contribute to stiffness-induced GEF-H1 activation in this context. 3D matrix stiffness assay, microtubule stability assay, GEF-H1 siRNA, RhoA activity assay, cell contraction/invasion assay Molecular biology of the cell Medium 22593214
2013 GEF-H1 is essential for RIG-I-like receptor sensing of foreign RNA; upon microtubule release GEF-H1 activation controls RIG-I- and Mda5-dependent IRF3 phosphorylation and IFN-β induction; Arhgef2−/− mice show pronounced antiviral signaling defects against encephalomyocarditis virus and influenza A virus. Arhgef2 knockout mouse generation, viral challenge, IRF3 phosphorylation assay, IFN-β induction assay, siRNA knockdown in macrophages Nature immunology High 24270516
2013 TNF-α sequentially activates Rac (via GEF-H1 phosphorylation at S885) and then RhoA (via GEF-H1 T678 phosphorylation) through a single exchange factor; GEF-H1-mediated Rac activation drives TACE/ADAM17, which transactivates EGFR/ERK and leads to T678 phosphorylation and RhoA activation. siRNA knockdown, phospho-specific western blots (T678, S885 mutants), Rac and RhoA activity assays, TACE activity assay Molecular biology of the cell High 23389627
2014 GEF-H1 acts as an adaptor linking PP2A B' subunits to the scaffold protein KSR-1, mediating dephosphorylation of KSR-1 S392 and activating MAPK signaling downstream of oncogenic RAS; this role is independent of GEF-H1's RhoGEF catalytic activity. Co-IP (GEF-H1–KSR-1–PP2A), phosphorylation assay, GEF-H1 catalytic mutant analysis, siRNA knockdown, tumor xenograft growth assay Cancer cell High 24525234
2014 MARK3 (activated by LKB1) phosphorylates ARHGEF2 at Ser151, generating a 14-3-3 binding site that disrupts the ARHGEF2–DYNLT1 (Tctex-1) interaction and dissociates ARHGEF2 from microtubules; this stimulates RhoA activation and stress fiber/focal adhesion formation; PP2A dephosphorylates Ser151 to restore the inhibited state. In vitro kinase assay (MARK3), Co-IP (ARHGEF2–DYNLT1, ARHGEF2–14-3-3), site-directed mutagenesis (S151), 3D culture architecture assay, phosphatase assay Science signaling High 29089450
2014 RASSF1A stimulates cofilin/PP2A-mediated dephosphorylation of GEF-H1, thereby activating GEF-H1 to activate the antimetastatic GTPase RhoB; RASSF1A loss reduces GEF-H1-mediated RhoB activation and increases nuclear YAP, promoting EMT and invasion. RNAi silencing, Co-IP, PP2A/cofilin phosphatase assay, RhoB activation assay, in vivo metastasis assay Cancer research Medium 26759237
2014 GEF-H1 mediates GEF-H1/RhoA activation induced by LPA or thrombin (GPCR ligands) through a mechanism independent of microtubule depolymerization: Gα directly binds GEF-H1 and displaces it from Tctex-1, while Gβγ binds Tctex-1 and disrupts its dynein intermediate chain interaction; full GEF-H1 activation requires subsequent PP2A-mediated dephosphorylation of Ser885. Co-IP (GEF-H1–Tctex-1–dynein, Gα–GEF-H1, Gβγ–Tctex-1), direct binding assay, GEF-H1 activity assay, phosphatase assay, LPA/thrombin stimulation Nature communications High 25209408
2014 GEF-H1 functions in apical constriction and cell intercalation during Xenopus neural tube closure; GEF-H1 depletion (morpholino) causes neural tube defects with impaired MLC phosphorylation, Rab11 and F-actin accumulation; overexpressed GEF-H1 induces ROCK-dependent ectopic apical constriction. Morpholino knockdown, RNA rescue, lineage tracing, MLC phosphorylation assay, ROCK inhibitor, immunofluorescence in Xenopus embryo Journal of cell science High 24681784
2015 VopO, a Vibrio parahaemolyticus type III effector, directly binds GEF-H1 via an alpha-helix region; this interaction is required for T3SS2-dependent RhoA-ROCK pathway activation and stress fiber formation; GEF-H1 binding activity of VopO correlates with its stress fiber-inducing and epithelial barrier disruption capacity. Direct pulldown (VopO–GEF-H1), Co-IP, deletion/mutagenesis mapping, RhoA activity assay, transepithelial resistance measurement PLoS pathogens High 25738744
2015 RalB (but not RalA) promotes TGFβ-induced cancer cell dissemination via GEF-H1; RalB acts through the exocyst subunit Sec5 to promote GEF-H1-dependent RhoA activation and actomyosin contractility; uncoupling Sec5 from GEF-H1 impairs RhoA activation and traction force generation. Co-IP (GEF-H1–Sec5), siRNA knockdown (RalA vs RalB), traction force microscopy, RhoA activation assay, 3D dissemination assay Scientific reports High 26152517
2016 The TRPC3 channel mediates mechanical stress/TGFβ-induced GEF-H1 activation in cardiomyocytes and cardiac fibroblasts; TRPC3 functionally interacts with microtubule-associated Nox2, and Nox2 inhibition attenuates mechanical stretch-induced GEF-H1 activation; TRPC3 inhibition suppresses GEF-H1-mediated RhoA activation and fibrotic responses. Proteomics (TRPC3 interactome), Nox2 inhibitor studies, GEF-H1 activation assay, fibrosis assays in cardiomyocytes/fibroblasts, pressure-overload mouse model Scientific reports Medium 27991560
2016 Autophagy degrades GEF-H1 via a p62-dependent mechanism; in autophagy-deficient cells (Atg5/Atg7/Ulk1 KO), GEF-H1 accumulates, RhoA activity increases, and cells switch to amoeboid migration; GEF-H1 silencing in Atg5 KO cells reverts this phenotype. Co-IP (GEF-H1–p62), Atg5/Atg7/Ulk1 knockout MEFs, GEF-H1 silencing rescue, RhoA activity assay, cell migration assay Oncotarget High 27120804
2016 PP2A regulatory subunit PPP2R2A binds, dephosphorylates, and activates GEF-H1 at Ser885, leading to increased RhoA-GTP levels and ROCK activity in T cells, promoting Th1 and Th17 differentiation. Co-IP (PPP2R2A–GEF-H1), phospho-Ser885 western blot, RhoA activity assay, T cell conditional knockout, Th1/Th17 differentiation assay Journal of immunology High 33762326
2017 Vimentin intermediate filaments regulate actin stress fiber assembly via GEF-H1; vimentin loss induces phosphorylation of GEF-H1 at Ser886, promoting RhoA activity and stress fiber assembly; this requires intact vimentin filaments (not unit-length forms). Vimentin knockout cells, wild-type vs non-filamentous vimentin rescue, Ser886 phosphorylation western blot, RhoA activity assay, MLC phosphorylation assay Journal of cell science High 28096473
2017 Homozygous frameshift mutation in ARHGEF2 causes intellectual disability and midbrain-hindbrain malformation; loss of ARHGEF2 perturbs progenitor cell differentiation, shifts mitotic spindle plane orientation toward symmetric divisions, and reduces RhoA/ROCK/MLC pathway activation; Arhgef2 mutant mice recapitulate the human malformation with aberrant precerebellar neuron migration. Whole exome sequencing, Arhgef2 knockout/mutant mouse, spindle orientation analysis, MLC phosphorylation assay, neuronal migration assay PLoS genetics High 28453519
2019 GEF-H1 contains an autoinhibitory sequence; live-cell biosensor imaging reveals that autoinhibited GEF-H1 localizes to microtubules, while MT depolymerization at the cell cortex activates GEF-H1 in a ~5-µm peripheral band; Src phosphorylation activates GEF-H1 in a narrower ~0-2 µm band at the cell edge in coordination with protrusions. GEF-H1 activation FRET biosensor, live-cell simultaneous imaging of MT dynamics and GEF-H1 activity, Src inhibitor treatment, autoinhibitory sequence mapping The Journal of cell biology High 31420453
2019 GEF-H1 is specifically released upon microtubule destabilization in dendritic cells and drives DC maturation via JNK pathway and AP-1/ATF transcriptional response; GEF-H1 promotes cross-presentation of tumor antigens to CD8 T cells; Arhgef2−/− mice show impaired anti-tumor immunity. Arhgef2 knockout mice, DC maturation assay, JNK activity assay, antigen cross-presentation assay, in vivo tumor challenge Cell reports High 31553907
2019 GEF-H1 is required for IKKε-mediated phosphorylation and activation of IRF5 in response to microbial muramyl-dipeptides; GEF-H1 functions in a microtubule-based peptidoglycan recognition system independent of NOD-like receptors; deletion or dominant-negative GEF-H1 prevents IKKε and IRF5 activation and host defenses against Listeria monocytogenes. GEF-H1 knockout/dominant-negative, IKKε kinase assay, IRF5 phosphorylation assay, Listeria infection model Nature communications High 30902986
2020 BNIP-2 (a BCH domain protein) binds both GEF-H1 and RhoA and traffics with kinesin-1 on microtubules; upon microtubule disassembly, the BNIP-2–GEF-H1 interaction increases and BNIP-2 scaffolds GEF-H1–RhoA coupling; BNIP-2 depletion reduces RhoA activation and cell rounding after nocodazole treatment. Co-IP (BNIP-2–GEF-H1, BNIP-2–RhoA), kinesin-1 trafficking assay, siRNA knockdown, RhoA activity assay, live-cell imaging Science advances High 32789168
2020 PKA and PKG phosphorylate GEF-H1 at Ser886 in platelets, stimulating 14-3-3β binding and promoting GEF-H1 association with microtubules, thereby inhibiting GEF-H1 GEF function; microtubule disruption increases RhoA-GTP levels in platelets, confirming GEF-H1's role in platelet RhoA regulation. Phosphoproteomics, western blot (Ser886 phosphorylation), Phos-tag gel, 14-3-3 binding pulldown, microtubule disruption assay, RhoA-GTP pulldown Journal of thrombosis and haemostasis Medium 32692911
2021 YTHDF1 binds m6A sites on ARHGEF2 mRNA, enhancing ARHGEF2 translation; increased ARHGEF2 protein activates RhoA signaling and promotes CRC tumor growth and metastasis; siRNA-LNP delivery targeting ARHGEF2 suppresses tumor growth in vivo. m6A-MeRIP-seq, YTHDF1 RIP-seq, proteomics, Ythdf1 knockout mouse (inflammatory CRC model), rescue with ARHGEF2 overexpression, siRNA-LNP in vivo treatment Gastroenterology High 34968454
2021 Glutamine deficiency triggers macropinocytosis in pancreatic cancer-associated fibroblasts via CaMKK2-AMPK signaling and ARHGEF2; ARHGEF2 is required for this stromal macropinocytic response, which supplies amino acids to both CAFs and tumor cells. siRNA/shRNA knockdown of ARHGEF2, CaMKK2-AMPK inhibition, macropinocytosis assay (imaging), amino acid measurement, xenograft tumor growth assay Cancer discovery Medium 33653692
2021 NEK9 directly phosphorylates ARHGEF2, activating RhoA and promoting gastric cancer cell motility; NEK9 is transcriptionally suppressed by miR-520f-3p, which is itself repressed by IL-6/STAT3 signaling, placing ARHGEF2 phosphorylation downstream of the IL-6-STAT3-NEK9 pathway. In vitro kinase assay (NEK9→ARHGEF2), GST pulldown, Co-IP, phosphoproteomics, miR-520f-3p luciferase reporter, ChIP, RhoA activation assay Theranostics High 33500736
2021 Bartonella effector BepC binds GEF-H1 via its N-terminal FIC domain (in a non-catalytic manner) and re-localizes GEF-H1 from microtubules to the plasma membrane; this GEF-H1-dependent mechanism activates RhoA/ROCK and triggers actin stress fiber formation and cell fragmentation in migrating endothelial cells. Interactomic analysis (Co-IP/MS), GEF-H1 knockout cell lines, BepC domain mapping/mutagenesis, ROCK inhibitor, immunofluorescence PLoS pathogens High 33508040
2022 Peptide inhibitors designed against the GEF-H1 autoregulatory C-terminal domain block RhoA/GEF-H1 binding in vitro and inhibit GEF-H1-dependent TGFβ-induced fibrosis, LPS-stimulated endothelial barrier disruption, and cell migration; the most potent inhibitor inhibits blood vessel leakage and retinal inflammation in an in vivo retinal disease model. In silico peptide design, in vitro RhoA/GEF-H1 binding assay, cell-based permeability and migration assays, in vivo retinal disease mouse model Cells Medium 35681428
2023 HUNK kinase directly phosphorylates GEF-H1 at Ser645, which activates RhoA and leads to cascading phosphorylation of LIMK-1/CFL-1, stabilizing F-actin and inhibiting EMT in colorectal cancer. In vitro kinase assay (HUNK→GEF-H1 S645), phospho-specific western blot, RhoA/LIMK-1/CFL-1 activity assays, siRNA/overexpression in CRC cells, in vivo metastasis model Cell death & disease High 37193711
2012 FAM123A binds to ARHGEF2 via a microtubule-associated interaction, and this binding inhibits ARHGEF2 GEF activity; FAM123A depletion increases actomyosin contractility, focal adhesion size, and decreases cell migration in an ARHGEF2-dependent manner. Affinity purification/mass spectrometry, domain interaction assay, siRNA knockdown, actomyosin contractility assay, focal adhesion size measurement, cell migration assay Science signaling Medium 22949735
2011 hPTTG1 transcriptionally activates GEF-H1 gene expression by directly binding and activating the GEF-H1 promoter (validated by luciferase reporter and ChIP); hPTTG1 knockdown decreases GEF-H1 expression and RhoA activation, reducing breast cancer cell motility and invasion, rescued by GEF-H1 re-expression. Luciferase reporter assay, ChIP assay, siRNA knockdown, RhoA activity assay, invasion/migration assay, in vivo metastasis model Oncogene High 22002306
2016 Tension on JAM-A activates RhoA via GEF-H1 (and p115 RhoGEF) through PI3K-mediated GEF-H1 activation; FAK/ERK further regulate GEF-H1; phosphorylation of JAM-A at Ser284 is required for this RhoA activation in response to tension. Magnetic bead tension application, PI3K inhibitor, siRNA knockdown of GEF-H1 and p115, RhoA activity assay, JAM-A phospho-mutant analysis Molecular biology of the cell Medium 26985018
2016 ONCOGENIC KRAS transcriptionally activates ARHGEF2 through a minimal RAS-responsive promoter regulated by ELK1, ETS1, SP1, SP3 (positive) and RREB1 (negative); RREB1 knockdown increases ARHGEF2 expression and extends RhoA activation duration; ARHGEF2 rescues SP3 loss-of-function invasion/migration defects. Promoter reporter assay, transcription factor ChIP/knockdown, ARHGEF2 overexpression rescue, RhoA activation assay, invasion/migration assay Oncotarget Medium 27835861

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton. Nature cell biology 548 11912491
2011 The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins. Nature cell biology 305 21572419
2008 GEF-H1 couples nocodazole-induced microtubule disassembly to cell contractility via RhoA. Molecular biology of the cell 284 18287519
1998 Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases. The Journal of biological chemistry 262 9857026
2007 GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases. Developmental cell 190 17488622
2005 Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1/S phase transition. Developmental cell 177 15866167
2020 Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis. Theranostics 172 32724467
1995 Expression cloning of lfc, a novel oncogene with structural similarities to guanine nucleotide exchange factors and to the regulatory region of protein kinase C. The Journal of biological chemistry 167 7629163
2021 N6-Methyladenosine Reader YTHDF1 Promotes ARHGEF2 Translation and RhoA Signaling in Colorectal Cancer. Gastroenterology 159 34968454
2008 Cellular functions of GEF-H1, a microtubule-regulated Rho-GEF: is altered GEF-H1 activity a crucial determinant of disease pathogenesis? Trends in cell biology 157 18394899
2004 p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a microtubule-localized Rho exchange factor. The Journal of biological chemistry 156 14970201
2017 Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA. Journal of cell science 150 28096473
2005 GEF-H1 is involved in agonist-induced human pulmonary endothelial barrier dysfunction. American journal of physiology. Lung cellular and molecular physiology 144 16257999
2005 PAK4 mediates morphological changes through the regulation of GEF-H1. Journal of cell science 143 15827085
1999 The Dbl-related protein, Lfc, localizes to microtubules and mediates the activation of Rac signaling pathways in cells. The Journal of biological chemistry 140 9890991
2004 Enteropathogenic Escherichia coli activates the RhoA signaling pathway via the stimulation of GEF-H1. The EMBO journal 129 15318166
1996 Lfc and Lsc oncoproteins represent two new guanine nucleotide exchange factors for the Rho GTP-binding protein. The Journal of biological chemistry 125 8910315
2005 The Rho-specific GEF Lfc interacts with neurabin and spinophilin to regulate dendritic spine morphology. Neuron 121 15996550
2016 RASSF1A Suppresses the Invasion and Metastatic Potential of Human Non-Small Cell Lung Cancer Cells by Inhibiting YAP Activation through the GEF-H1/RhoB Pathway. Cancer research 100 26759237
2008 GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. PLoS pathogens 99 19043560
2021 Macropinocytosis in Cancer-Associated Fibroblasts Is Dependent on CaMKK2/ARHGEF2 Signaling and Functions to Support Tumor and Stromal Cell Fitness. Cancer discovery 96 33653692
2010 Mechanotransduction by GEF-H1 as a novel mechanism of ventilator-induced vascular endothelial permeability. American journal of physiology. Lung cellular and molecular physiology 94 20348280
2006 Mutant p53 induces the GEF-H1 oncogene, a guanine nucleotide exchange factor-H1 for RhoA, resulting in accelerated cell proliferation in tumor cells. Cancer research 92 16778209
2009 GEF-H1 mediates tumor necrosis factor-alpha-induced Rho activation and myosin phosphorylation: role in the regulation of tubular paracellular permeability. The Journal of biological chemistry 86 19261619
2014 The RhoGEF GEF-H1 is required for oncogenic RAS signaling via KSR-1. Cancer cell 85 24525234
2008 Paracingulin regulates the activity of Rac1 and RhoA GTPases by recruiting Tiam1 and GEF-H1 to epithelial junctions. Molecular biology of the cell 82 18653465
2012 Microtubules regulate GEF-H1 in response to extracellular matrix stiffness. Molecular biology of the cell 81 22593214
2010 The RhoA activator GEF-H1/Lfc is a transforming growth factor-beta target gene and effector that regulates alpha-smooth muscle actin expression and cell migration. Molecular biology of the cell 81 20089843
2009 Lfc and Tctex-1 regulate the genesis of neurons from cortical precursor cells. Nature neuroscience 75 19448628
2008 ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange activity toward RhoA. Biochemical and biophysical research communications 74 18211802
2016 TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis. Scientific reports 71 27991560
2009 AMPA receptor and GEF-H1/Lfc complex regulates dendritic spine development through RhoA signaling cascade. Proceedings of the National Academy of Sciences of the United States of America 65 19208802
2009 Modulation of Rho guanine exchange factor Lfc activity by protein kinase A-mediated phosphorylation. Molecular and cellular biology 63 19667072
2011 The epidermal growth factor receptor mediates tumor necrosis factor-alpha-induced activation of the ERK/GEF-H1/RhoA pathway in tubular epithelium. The Journal of biological chemistry 60 21212278
2011 Overexpressed hPTTG1 promotes breast cancer cell invasion and metastasis by regulating GEF-H1/RhoA signalling. Oncogene 60 22002306
2014 Mechanistic insight into GPCR-mediated activation of the microtubule-associated RhoA exchange factor GEF-H1. Nature communications 59 25209408
2019 GEF-H1 Signaling upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-tumor Responses. Cell reports 57 31553907
2005 The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis. Proceedings of the National Academy of Sciences of the United States of America 56 15976019
2012 The microtubule-associated Rho activating factor GEF-H1 interacts with exocyst complex to regulate vesicle traffic. Developmental cell 55 22898781
2011 Polarity-regulating kinase partitioning-defective 1b (PAR1b) phosphorylates guanine nucleotide exchange factor H1 (GEF-H1) to regulate RhoA-dependent actin cytoskeletal reorganization. The Journal of biological chemistry 53 22072711
2006 TRIF-GEFH1-RhoB pathway is involved in MHCII expression on dendritic cells that is critical for CD4 T-cell activation. The EMBO journal 53 16917499
2019 Spatiotemporal dynamics of GEF-H1 activation controlled by microtubule- and Src-mediated pathways. The Journal of cell biology 52 31420453
2020 Regulation and functions of the RhoA regulatory guanine nucleotide exchange factor GEF-H1. Small GTPases 46 33126816
2017 MARK3-mediated phosphorylation of ARHGEF2 couples microtubules to the actin cytoskeleton to establish cell polarity. Science signaling 46 29089450
2009 The Y-box factor ZONAB/DbpA associates with GEF-H1/Lfc and mediates Rho-stimulated transcription. EMBO reports 46 19730435
2014 TGF-β regulates LARG and GEF-H1 during EMT to affect stiffening response to force and cell invasion. Molecular biology of the cell 45 25143398
2012 GEF-H1-RhoA signaling pathway mediates LPS-induced NF-κB transactivation and IL-8 synthesis in endothelial cells. Molecular immunology 45 22226472
2013 GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses. Nature immunology 44 24270516
2010 Extracellular signal-regulated kinase and GEF-H1 mediate depolarization-induced Rho activation and paracellular permeability increase. American journal of physiology. Cell physiology 44 20237148
2014 GEF-H1 functions in apical constriction and cell intercalations and is essential for vertebrate neural tube closure. Journal of cell science 41 24681784
2012 GEF-H1 over-expression in hepatocellular carcinoma promotes cell motility via activation of RhoA signalling. The Journal of pathology 39 22847784
2012 Vincristine enhances amoeboid-like motility via GEF-H1/RhoA/ROCK/Myosin light chain signaling in MKN45 cells. BMC cancer 39 23057787
2011 Calpain-6, a microtubule-stabilizing protein, regulates Rac1 activity and cell motility through interaction with GEF-H1. Journal of cell science 39 21406564
2010 Involvement of p114-RhoGEF and Lfc in Wnt-3a- and dishevelled-induced RhoA activation and neurite retraction in N1E-115 mouse neuroblastoma cells. Molecular biology of the cell 38 20810787
2021 NEK9, a novel effector of IL-6/STAT3, regulates metastasis of gastric cancer by targeting ARHGEF2 phosphorylation. Theranostics 37 33500736
2012 Heparanase-induced GEF-H1 signaling regulates the cytoskeletal dynamics of brain metastatic breast cancer cells. Molecular cancer research : MCR 37 22513363
2014 Stiffness-activated GEF-H1 expression exacerbates LPS-induced lung inflammation. PloS one 36 24739883
2011 Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1. Inflammatory bowel diseases 36 21887730
2016 Tension on JAM-A activates RhoA via GEF-H1 and p115 RhoGEF. Molecular biology of the cell 35 26985018
2013 Central role of the exchange factor GEF-H1 in TNF-α-induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells. Molecular biology of the cell 35 23389627
2011 Dynamic regulation of GEF-H1 localization at microtubules by Par1b/MARK2. Biochemical and biophysical research communications 35 21513698
2014 Paxillin mediates stretch-induced Rho signaling and endothelial permeability via assembly of paxillin-p42/44MAPK-GEF-H1 complex. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34 24706358
2013 Non-centrosomal microtubules regulate F-actin organization through the suppression of GEF-H1 activity. Genes to cells : devoted to molecular & cellular mechanisms 34 23432781
2013 Control of vascular permeability by atrial natriuretic peptide via a GEF-H1-dependent mechanism. The Journal of biological chemistry 34 24352660
2021 The Regulatory Subunit PPP2R2A of PP2A Enhances Th1 and Th17 Differentiation through Activation of the GEF-H1/RhoA/ROCK Signaling Pathway. Journal of immunology (Baltimore, Md. : 1950) 33 33762326
2018 A role for RASSF1A in tunneling nanotube formation between cells through GEFH1/Rab11 pathway control. Cell communication and signaling : CCS 33 30305100
2010 Evidence for the involvement of Lfc and Tctex-1 in axon formation. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 20463241
2010 Modulation of GEF-H1 induced signaling by heparanase in brain metastatic melanoma cells. Journal of cellular biochemistry 32 20803552
2015 RalB regulates contractility-driven cancer dissemination upon TGFβ stimulation via the RhoGEF GEF-H1. Scientific reports 31 26152517
2014 GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment. Journal of cell science 31 25107365
2012 GEF-H1/RhoA signalling pathway mediates lipopolysaccharide-induced intercellular adhesion molecular-1 expression in endothelial cells via activation of p38 and NF-κB. Cytokine 29 22226621
2019 Claudin-2 suppresses GEF-H1, RHOA, and MRTF, thereby impacting proliferation and profibrotic phenotype of tubular cells. The Journal of biological chemistry 27 31481470
2017 Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation. PLoS genetics 27 28453519
2022 ARHGEF2/EDN1 pathway participates in ER stress-related drug resistance of hepatocellular carcinoma by promoting angiogenesis and malignant proliferation. Cell death & disease 25 35896520
2021 S-1-propenylcysteine improves TNF-α-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1/RhoA/Rac pathway. Cell communication and signaling : CCS 25 33588881
2020 BNIP-2 retards breast cancer cell migration by coupling microtubule-mediated GEF-H1 and RhoA activation. Science advances 25 32789168
2020 FAK regulates actin polymerization during sperm capacitation via the ERK2/GEF-H1/RhoA signaling pathway. Journal of cell science 24 32107290
2015 Interaction between the type III effector VopO and GEF-H1 activates the RhoA-ROCK pathway. PLoS pathogens 24 25738744
2010 Mutant huntingtin alters cell fate in response to microtubule depolymerization via the GEF-H1-RhoA-ERK pathway. The Journal of biological chemistry 23 20858895
2019 High-grade glioneuronal tumor with an ARHGEF2-NTRK1 fusion gene. Brain tumor pathology 22 31011918
2016 Autophagy suppresses cell migration by degrading GEF-H1, a RhoA GEF. Oncotarget 22 27120804
2013 GEF-H1: orchestrating the interplay between cytoskeleton and vesicle trafficking. Small GTPases 22 23648943
2022 Microtubules restrict F-actin polymerization to the immune synapse via GEF-H1 to maintain polarity in lymphocytes. eLife 20 36111670
2018 Rotenone inhibits axonogenesis via an Lfc/RhoA/ROCK pathway in cultured hippocampal neurons. Journal of neurochemistry 20 29972689
2005 Activation of gef-h1, a guanine nucleotide exchange factor for RhoA, by DNA transfection. International journal of cancer 20 15455375
2019 Increased expression of GEF-H1 promotes colon cancer progression by RhoA signaling. Pathology, research and practice 19 30846413
2019 The GEF-H1/PKD3 signaling pathway promotes the maintenance of triple-negative breast cancer stem cells. International journal of cancer 19 31745977
2017 An oncogenic KRAS transcription program activates the RHOGEF ARHGEF2 to mediate transformed phenotypes in pancreatic cancer. Oncotarget 19 27835861
2016 p66Shc Couples Mechanical Signals to RhoA through Focal Adhesion Kinase-Dependent Recruitment of p115-RhoGEF and GEF-H1. Molecular and cellular biology 19 27573018
2020 The RhoA regulators Myo9b and GEF-H1 are targets of cyclic nucleotide-dependent kinases in platelets. Journal of thrombosis and haemostasis : JTH 18 32692911
2017 GSK-3Beta-Dependent Activation of GEF-H1/ROCK Signaling Promotes LPS-Induced Lung Vascular Endothelial Barrier Dysfunction and Acute Lung Injury. Frontiers in cellular and infection microbiology 18 28824887
2016 miR-194 is a negative regulator of GEF-H1 pathway in melanoma. Oncology reports 17 27573550
2023 HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1. Cell death & disease 16 37193711
2011 GEFH1 binds ASAP1 and regulates podosome formation. Biochemical and biophysical research communications 16 21352810
2021 Bartonella effector protein C mediates actin stress fiber formation via recruitment of GEF-H1 to the plasma membrane. PLoS pathogens 15 33508040
2019 Microbial recognition by GEF-H1 controls IKKε mediated activation of IRF5. Nature communications 14 30902986
2012 FAM123A binds to microtubules and inhibits the guanine nucleotide exchange factor ARHGEF2 to decrease actomyosin contractility. Science signaling 14 22949735
2017 Go with the flow: GEF-H1 mediated shear stress mechanotransduction in neutrophils. Small GTPases 13 29188751
2015 Dexamethasone-induced cellular tension requires a SGK1-stimulated Sec5-GEF-H1 interaction. Journal of cell science 13 26359301
2022 Therapeutic Validation of GEF-H1 Using a De Novo Designed Inhibitor in Models of Retinal Disease. Cells 11 35681428

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