| 1998 |
ARHGEF7 (PIX/Cool-1) was identified as a guanine nucleotide exchange factor that binds tightly to PAK kinases through its N-terminal SH3 domain interacting with a conserved proline-rich PAK sequence (Kd ~24 nM). PIX is enriched in Cdc42- and Rac1-driven focal complexes, is required for PAK recruitment to these sites, and can induce membrane ruffling with associated Rac1 activation, suggesting a role in Cdc42-to-Rac1 signaling. |
Protein purification, cloning, binding assays, co-localization in focal complexes, membrane ruffling assays |
Molecular cell |
High |
9659915
|
| 1998 |
ARHGEF7 (Cool-1) was identified as a PAK3-binding protein with SH3, DH, and PH domains. The p50 isoform binding to PAK3 represses PAK3 activation by upstream activators such as the Dbl oncoprotein, revealing a novel regulatory mechanism for PAK signaling; the p85 isoform did not show this repressive activity. |
Library cloning, co-immunoprecipitation, kinase activity assays, isoform comparison |
The Journal of biological chemistry |
High |
9726964
|
| 1999 |
ARHGEF7 (PIX) is recruited to focal adhesions as part of a complex with PAK, Nck, and the scaffolding protein p95PKL (paxillin-kinase linker), which bridges PIX to the paxillin LD4 motif. This paxillin–p95PKL–PIX–PAK complex links paxillin to p21 GTPase-regulated actin cytoskeletal reorganization at focal adhesions. |
Co-immunoprecipitation, pulldown, GFP localization, dominant-negative overexpression, microinjection with cell migration assay |
The Journal of cell biology |
High |
10330411
|
| 2010 |
ARHGEF7 (β-PIX) forms a complex with podocalyxin, EBP50 (ERM-binding phosphoprotein 50), and ezrin, which activates Rac1 to promote cell migration. Podocalyxin knockdown reduced Rac1 activity and migration; re-expression restored them. Podocalyxin overexpression in HEK cells upregulated Rac1 activity in an ARHGEF7-dependent manner. |
siRNA knockdown, co-immunoprecipitation, Rac1 activity assay (GST-PAK pulldown), overexpression rescue |
The American journal of pathology |
High |
20395446
|
| 2010 |
ARHGEF7 (β-PIX) interacts with LRRK2 in vitro and in vivo, acts as a guanine nucleotide exchange factor for LRRK2 (stimulating its GTPase activity), and is phosphorylated by LRRK2 at previously unknown sites. The Parkinson's disease-associated R1441C LRRK2 mutant shows reduced GTP hydrolysis and reduced binding to ARHGEF7. |
Co-immunoprecipitation, in vitro GTPase activity assay, in vitro kinase assay, phosphorylation site mapping, mutant binding studies |
PloS one |
High |
21048939
|
| 2011 |
ARHGEF7 (β-PIX) localizes to focal adhesions and negatively regulates focal adhesion maturation. It is enriched in focal adhesions upon myosin II inhibition (conditions favoring Rac-mediated lamellipodia), and promotes lamellipodial protrusion and focal adhesion turnover to drive cell migration. Its abundance in focal adhesions is inversely regulated by myosin II-driven contractility. |
Proteomic analysis of isolated focal adhesions, quantitative MS comparison ±myosin II inhibition, live-cell imaging, knockdown with defined phenotypic readouts |
Nature cell biology |
High |
21423176
|
| 2012 |
ARHGEF7 is a Rac1-specific effector pathway component negatively regulated by CYK4 GAP activity during cytokinesis. The MKlp1-CYK4 centralspindlin complex acts as a GAP for Rac1 (not RhoA) at the cell equator in anaphase. Depletion of ARHGEF7 rescued cytokinesis defects and elevated vinculin/adhesion phenotypes caused by expression of a CYK4 GAP mutant, demonstrating that CYK4 inhibits ARHGEF7-dependent cell adhesion pathways to spatially segregate adhesion from contractile ring formation. |
siRNA depletion, rescue genetics (epistasis), immunofluorescence for vinculin, GAP activity assays |
The Journal of cell biology |
High |
22945935
|
| 2013 |
In LRRK2-knockdown primary hippocampal neurons, ARHGEF7 is mislocalized and dysregulated at growth cones, leading to enhanced neurite branching and increased growth cones per neuron. ARHGEF7 and Tropomyosin 4 (TPM4) co-regulate actin polymerization at growth cones downstream of LRRK2, with LRRK2 knockdown and ARHGEF7 knockdown showing convergent effects on neurite outgrowth. |
LRRK2 knockdown in primary neurons, transcriptome profiling, immunofluorescence localization, neurite morphology quantification |
Biochimica et biophysica acta |
Medium |
24075941
|
| 2014 |
CK1α phosphorylates LRRK2, and this phosphorylation modulates LRRK2 recruitment to TGN46-positive Golgi-derived vesicles through differential interaction with ARHGEF7. Constitutive LRRK2 phosphorylation by CK1α regulates trans-Golgi clustering via altered ARHGEF7 binding, placing ARHGEF7 in a CK1α→LRRK2→ARHGEF7 signaling axis for Golgi maintenance. |
siRNA kinome screen, co-immunoprecipitation, subcellular fractionation/localization, phosphorylation assays |
Nature communications |
High |
25500533
|
| 2014 |
ARHGEF7 (βPix) binds both LATS kinase and YAP/TAZ and acts as a positive regulator of the Hippo pathway by scaffolding LATS-mediated phosphorylation of YAP/TAZ in a GEF-independent manner. βPix localizes to the cytoplasm and is required downstream of both cell density sensing and actin cytoskeletal rearrangements. Loss of βPix reduces YAP/TAZ phosphorylation and promotes nuclear YAP/TAZ localization and target gene expression; conversely, increased βPIX in breast cancer cell lines restores cytoplasmic YAP/TAZ and inhibits migration and proliferation. |
Co-immunoprecipitation, phosphorylation assays, knockdown/overexpression, nuclear/cytoplasmic fractionation, reporter assays, GEF-dead mutant analysis |
The EMBO journal |
High |
25425573
|
| 2018 |
Arhgef7 is essential for axon formation during cortical development. Loss of Arhgef7 causes extensive loss of axons in cultured neurons and in the developing cortex. Although Arhgef7 is a known GEF for Cdc42, active Cdc42 could not rescue Arhgef7 knockdown. Instead, Arhgef7 was found to interact with and act upstream of the GTPase TC10 (closely related to Cdc42), and expression of active TC10 restored axon extension in Arhgef7-deficient neurons. |
In utero electroporation knockdown, cultured neuron morphology, rescue experiments with active GTPases, co-immunoprecipitation |
Scientific reports |
High |
29891904
|
| 2019 |
ARHGEF7 forms a ternary complex with STIL and PAK1 that accumulates at lamellipodia of migrating cancer cells. STIL knockdown impairs accumulation of the ARHGEF7-PAK1 complex at membrane ruffles, reduces PAK1 substrate phosphorylation, and attenuates cortical actin remodeling. ARHGEF7 knockdown similarly reduces STIL and PAK1 accumulation at membrane ruffles and diminishes Rac1 activity at the leading edge, implicating STIL in ARHGEF7-mediated positive-feedback Rac1 activation for polarized cell migration. |
Co-immunoprecipitation, siRNA knockdown, immunofluorescence localization, PAK1 substrate phosphorylation assay, Rac1 activity assay |
Oncogene |
High |
31754215
|
| 2020 |
ARHGEF7 (β-PIX) is a predominant GEF that activates Cdc42 in human podocytes, identified by proximity-ligation BioID. Podocyte-specific β-PIX knockout mice develop progressive proteinuria and glomerulosclerosis with podocyte loss. Loss of β-PIX reduces Cdc42 activity in podocytes and promotes podocyte apoptosis via reduced activity of the pro-survival transcriptional regulator YAP (Yes-associated protein). |
BioID proximity ligation, conditional knockout mice, Cdc42 activity assay, shRNA knockdown, apoptosis assays, YAP activity measurement |
Journal of the American Society of Nephrology : JASN |
High |
32188698
|
| 2020 |
ARHGEF7 is targeted for ubiquitin-proteasome degradation by the E3 ubiquitin ligase KLHL2. The Kelch domain of KLHL2 is necessary for binding ARHGEF7. KLHL2 overexpression promotes ARHGEF7 ubiquitination and degradation; KLHL2 and ARHGEF7 expression levels are inversely correlated in clear cell renal cell carcinoma. |
Co-immunoprecipitation, ubiquitination assays, proteasome inhibitor treatment, domain deletion mapping, knockdown/overexpression functional assays |
American journal of cancer research |
High |
33163274
|
| 2024 |
The β-PIX-d isoform of ARHGEF7 activates Rac1 and induces neuritogenesis in primary cortical neurons. Overexpression of β-PIX-d in the embryonic neocortex induced neuronal clustering and enhanced neurite outgrowth with misplacement of layer V-VI neurons. In primary neocortical cultures, β-PIX-d overexpression increased Rac1 activity as detected by GST-PAK pulldown assays. |
In utero electroporation, histological analysis, layer-specific marker immunofluorescence, Rac1 activity pulldown assay |
Experimental neurobiology |
Medium |
39568178
|
| 2025 |
Arhgef7 is expressed in granule cell precursors (GCPs) of the developing cerebellum and is essential for GCP proliferation, migration, and differentiation. Conditional knockout of Arhgef7 in GCPs causes severe cerebellar hypoplasia, foliation defects (especially lobules VI/VII), reduced postnatal GCP proliferation, disorganized cell layers, delayed differentiation, and impaired tangential and radial migration. |
Conditional knockout mice (cKO), histology, immunofluorescence, cell proliferation assays, migration quantification |
iScience |
High |
41585483
|
| 2025 |
Arhgef7 in medial prefrontal cortex neurons is essential for dendritic and synaptic maintenance and protects cortical neurons from β-amyloid toxicity by activating the Wnt signaling pathway. Overexpression of Arhgef7 in mPFC neurons enhanced dendritic and synaptic growth and alleviated spatial cognitive impairments; knockdown caused opposite effects. Wnt pathway activation was identified as the downstream mechanism. |
Transcriptome sequencing, in vivo knockdown and overexpression (viral vectors), behavioral tests, neuropathological analysis, Wnt pathway reporter assays |
Alzheimer's research & therapy |
Medium |
40598577
|
| 2026 |
ARHGEF7 (β-PIX) regulates actomyosin-mediated exocytosis of von Willebrand factor (VWF) from Weibel-Palade bodies in endothelial cells. β-PIX depletion reduces WPB fusion events, prolongs VWF secretion post-fusion, and delays exocytic actomyosin ring kinetics. Domain analysis showed the PAK-interacting and GEF domains mediate cytoskeletal remodeling, while full-length β-PIX is required for VWF secretion. β-PIX regulates both septin ring formation and cofilin-mediated actin remodeling during actomyosin ring function. |
siRNA knockdown, live-cell imaging (GFP-VWF), truncated mutant rescue, septin and cofilin localization analysis |
Molecular biology of the cell |
High |
42024489
|