Affinage

SORBS3

Vinexin · UniProt O60504

Length
671 aa
Mass
75.3 kDa
Annotated
2026-06-10
46 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SORBS3 (vinexin) is a multi-SH3-domain adaptor protein that couples the actin cytoskeleton and focal adhesions to signaling, transcription, and mechanotransduction (PMID:9885244, PMID:24554436). It binds vinculin through its first and second SH3 domains and through an amphipathic H2 helix that contacts the vinculin D1b subdomain, building a talin–vinculin–vinexin ternary complex; on rigid ECM this interaction drives an 'open' vinculin conformation and promotes nuclear translocation of YAP/TAZ, defining vinexin as a stiffness mechanosensor at focal adhesions (PMID:9885244, PMID:24554436, PMID:30578314). Its third SH3 domain serves as a hub for distinct partners—Sos to control JNK/SAPK activation downstream of growth factors (PMID:10585480), the E3 ligase c-Cbl to sustain EGFR phosphorylation (PMID:16923119), and Rhotekin, which vinexin recruits to the midbody to enable cytokinetic abscission (PMID:19294487, PMID:28118077). Vinexin function is gated by phosphorylation: ERK1/2 directly phosphorylates the linker region at Ser189 (Ser593 in the α isoform), and this spatiotemporally regulated event shifts vinexin between promoting cell spreading/migration and inhibiting anchorage-independent growth (PMID:15184391, PMID:17486060, PMID:17241162), while v-Src-mediated tyrosine phosphorylation attenuates vinexin–vinculin binding (PMID:19580787). Beyond adhesion, vinexin acts in transcriptional and signaling control—inhibiting RARγ-mediated transcription by binding its non-phosphorylated AF-1 domain (PMID:15734736), protecting against cardiac hypertrophy by blocking AKT signaling (PMID:23429936), and negatively regulating autophagy by restraining an F-actin–AMOT–YAP/TAZ axis (PMID:34848853, PMID:35822241). Vinexin is required for keratinocyte migration and cutaneous wound healing in vivo, acting upstream of EGFR (PMID:20361963). SORBS3 abundance is itself controlled by UBE2T-mediated ubiquitination and proteasomal degradation, which de-represses IL-6/STAT3 signaling in lung adenocarcinoma (PMID:38816989).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Establishing vinexin as a vinculin-binding focal adhesion adaptor defined its core cytoskeletal scaffolding role and its capacity to remodel adhesions.

    Evidence Yeast two-hybrid, in vitro binding, immunofluorescence, and overexpression morphology in fibroblasts/epithelial cells

    PMID:9885244

    Open questions at the time
    • Did not resolve how vinexin alters vinculin conformation or force transmission
    • Functional consequences of cell-cell junction localization left undefined
  2. 1999 High

    Identifying Sos binding to the third SH3 domain and growth-factor-regulated complex disruption connected vinexin to JNK/SAPK signaling and showed its SH3 domains are functionally distinct signaling docks.

    Evidence In vitro binding, co-IP, phosphatase treatment, dominant-negative SH3 mutant, JNK/SAPK kinase assay

    PMID:10585480

    Open questions at the time
    • Did not establish the in vivo physiological pathway downstream of JNK activation
    • Selectivity for JNK over ERK mechanistically unexplained
  3. 2002 Medium

    Demonstrating linker-dependent, PKA-PAK-mediated anchorage-independent ERK2 activation showed vinexin can confer growth signaling independent of adhesion.

    Evidence Deletion mutants, dominant-negative constructs, H89 inhibitor, ERK2 assays in suspension vs adherent cells

    PMID:11825889

    Open questions at the time
    • Direct biochemical link from the linker region to PKA/PAK not established
    • Physiological context of anchorage-independent signaling untested in vivo
  4. 2004 High

    Identifying ERK as a direct vinexin kinase that docks via a DEF motif and phosphorylates Ser189 placed vinexin in a feedback loop with the MAPK pathway it helps activate.

    Evidence In vitro kinase assay, Ser189 mutagenesis, DEF-domain mapping, co-IP, immunofluorescence

    PMID:15184391

    Open questions at the time
    • Functional consequence of Ser189 phosphorylation not yet defined here
    • Whether ERK docking competes with other linker functions unknown
  5. 2005 High

    Showing vinexin β inhibits RARγ transcription by binding the non-phosphorylated AF-1 domain extended vinexin's role into nuclear receptor-dependent transcriptional control.

    Evidence Yeast two-hybrid, co-IP, immunofluorescence, gain/loss-of-function transcriptional reporters in F9 cells

    PMID:15734736

    Open questions at the time
    • Mechanism by which a cytoskeletal adaptor accesses the nucleus not resolved
    • Whether endogenous retinoid signaling is regulated this way in vivo untested
  6. 2006 Medium

    Linking vinexin β to c-Cbl sequestration that sustains EGFR phosphorylation, and to PKA-dependent WAVE2 stabilization, defined how vinexin shapes receptor signaling and actin-nucleation machinery.

    Evidence Phospho-Western, mutational analysis, siRNA, co-IP, subcellular fractionation, proteasome/PKA modulation

    PMID:16483316 PMID:16923119

    Open questions at the time
    • Direct demonstration that membrane c-Cbl is catalytically diverted not shown
    • PKA-to-WAVE2 stabilization mechanism only pharmacologically inferred
  7. 2007 Medium

    Showing Ser189 phosphorylation is spatially partitioned to the leading edge and functionally switches vinexin β between migration and anchorage-independent growth control gave a spatiotemporal logic to ERK-vinexin signaling.

    Evidence Phospho-state-specific antibody imaging, phosphomimetic/non-phosphorylatable mutants, spreading/migration/soft-agar assays

    PMID:17241162 PMID:17486060

    Open questions at the time
    • Upstream cue determining where phosphorylation occurs not identified
    • Neuronal synaptic role of Ser593 phosphorylation functionally unexplored
  8. 2009 Medium

    Mapping Rhotekin binding to the third SH3 domain and showing v-Src tyrosine phosphorylation weakens vinexin-vinculin binding revealed both new partners and phospho-regulation of the core adhesion interaction.

    Evidence Yeast two-hybrid, in vitro binding, co-IP from cells and brain, mutagenesis of phospho-sites, affinity comparison

    PMID:19294487 PMID:19580787

    Open questions at the time
    • Functional output of vinexin-Rhotekin at focal adhesions not yet defined here
    • Physiological kinase responsible for the three tyrosines not identified
  9. 2010 High

    Knockout mouse and knockdown studies established vinexin as physiologically required for keratinocyte migration and wound healing, acting upstream of EGFR.

    Evidence siRNA, scratch assay, pharmacological epistasis (AG1478, U0126), knockout mice, in vivo wound healing

    PMID:20361963

    Open questions at the time
    • Molecular mechanism by which vinexin promotes EGFR activation in migration unresolved
    • Tissue specificity of the wound-healing requirement not defined
  10. 2013 High

    In vivo cardiac and zebrafish models showed vinexin restrains AKT signaling to limit cardiac hypertrophy and integrates ErbB/MAPK signaling for neurogenesis, broadening its organismal roles.

    Evidence Transgenic/knockout mice, aortic banding, echocardiography; zebrafish ouchless mutant, erbb3 epistasis, MEK inhibition

    PMID:23429936 PMID:24004948

    Open questions at the time
    • Direct biochemical mechanism of AKT inhibition by vinexin not established
    • Zebrafish ErbB-MAPK-neurogenin1 link inferred genetically, not biochemically
  11. 2014 High

    FRAP-based stiffness assays and stress-granule studies defined vinexin as an ECM stiffness sensor and a stress-responsive component that relocalizes from adhesions during stress.

    Evidence Vinexin siRNA, vinculin PRL mutants, FRAP, stiffness migration assays; CPEB4 co-IP, FA-to-SG translocation, JNK inhibition, survival assay

    PMID:24554436 PMID:25237887

    Open questions at the time
    • How vinexin physically reports stiffness to vinculin not yet resolved at this stage
    • Functional contribution of vinexin within stress granules incompletely defined
  12. 2015 High

    Mapping the HCV NS5A interaction to the third SH3 domain (W307/Y325) and showing vinexin β controls NS5A hyperphosphorylation and HCV replication revealed a pathogen co-option of the adaptor.

    Evidence Reciprocal co-IP, interface mutagenesis on both partners, shRNA, HCV replication and rescue assays

    PMID:25972535

    Open questions at the time
    • How vinexin promotes CK1α-dependent NS5A phosphorylation mechanistically unclear
    • Whether host substrates are similarly regulated not addressed
  13. 2017 Medium

    Reconstitution of individual SORBS proteins and midbody studies distinguished vinexin α's vinculin-centric mechanosensing from ArgBP2's α-actinin role and assigned vinexin a cytokinetic abscission function via Rhotekin recruitment.

    Evidence Reconstituted MEF lines, traction force microscopy, FA morphometry; midbody immunofluorescence, siRNA, mutant lacking Rhotekin motif, time-lapse imaging

    PMID:28118077 PMID:28864765

    Open questions at the time
    • Structural basis for SORBS family functional divergence not resolved
    • How vinexin is targeted to the midbody not defined
  14. 2018 Medium

    Identifying vinexin α (with CAP) as required for vinculin-cytoskeleton association and stiffness-dependent YAP/TAZ nuclear localization in MSCs connected vinexin mechanosensing to transcriptional/differentiation outputs.

    Evidence siRNA, rigid/soft substrates, vinculin-cytoskeleton imaging, YAP/TAZ fractionation, MSC differentiation assays

    PMID:30068914

    Open questions at the time
    • YAP/TAZ-independent control of adipogenesis by vinexin mechanistically unexplained
    • Quantitative contribution relative to CAP not resolved
  15. 2019 High

    Defining the H2 amphipathic helix as a second vinculin-binding site that drives stiffness-dependent vinculin opening and YAP/TAZ translocation provided the structural mechanism of vinexin mechanosensing.

    Evidence H2 mutagenesis, in vitro binding, FRET vinculin conformation assay, stiffness-dependent YAP/TAZ localization

    PMID:30578314

    Open questions at the time
    • High-resolution structure of the talin-vinculin-vinexin complex not determined
    • How force is sensed and transmitted through H2 not directly measured
  16. 2021 Medium

    Establishing vinexin as a negative autophagy regulator via an F-actin-AMOT-YAP/TAZ axis, with rising expression in aged brain, linked it to age-associated autophagic decline.

    Evidence siRNA, autophagy flux, F-actin imaging, YAP/TAZ localization, YAP/TAZ-AMOT co-IP, transcriptomics; aged brain expression analysis

    PMID:34848853 PMID:35822241

    Open questions at the time
    • Whether vinexin directly regulates F-actin or AMOT binding not shown
    • Causal role of vinexin in age-related autophagy decline in vivo not established
  17. 2024 Medium

    Showing UBE2T ubiquitinates and degrades SORBS3 to de-repress IL-6/STAT3 signaling defined a degradation mechanism controlling vinexin abundance in cancer, and SORBS3-β-driven β-catenin ubiquitination via UBA1 extended this to Wnt suppression.

    Evidence Co-IP, ubiquitination assays, knockdown/overexpression, xenograft models; LC-MS/MS and RNA-seq for the β-catenin axis

    PMID:38816989 PMID:40200335

    Open questions at the time
    • Direct E3 ligase partnering UBE2T toward SORBS3 not identified
    • Whether SORBS3-β acts as a bona fide ubiquitin adaptor for UBA1/β-catenin needs structural validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How vinexin's distinct activities—mechanosensing, MAPK/AKT/STAT signaling, transcriptional control, autophagy, and ubiquitin-dependent degradation—are integrated and switched in a given cell remains unresolved.
  • No unifying model coordinating focal-adhesion vs nuclear vs degradative functions
  • No high-resolution structure of vinexin in any of its complexes
  • Endogenous physiological triggers selecting among partner interactions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0008092 cytoskeletal protein binding 4 GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 1
Localization
GO:0005856 cytoskeleton 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-1474244 Extracellular matrix organization 4 R-HSA-162582 Signal Transduction 4 R-HSA-9612973 Autophagy 2 R-HSA-1640170 Cell Cycle 1 R-HSA-74160 Gene expression (Transcription) 1
Partners
CBLCPEB4CTNNB1ERK2/MAPK1RTKNSOS1VCLWASF2
Complex memberships
talin-vinculin-vinexin focal adhesion complexvinexin-vinculin-lp-dlg-β-catenin adherens junction complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Vinexin (SORBS3) was identified as a vinculin-binding protein; the interaction is mediated by the first and second SH3 domains of vinexin binding to the proline-rich hinge region of vinculin. Both vinexin α and β localize to focal adhesions in fibroblasts and cell-cell junctions in epithelial cells. Expression of vinexin increases focal adhesion size, promotes actin stress fiber formation (vinexin α), and enhances cell spreading on fibronectin. Yeast two-hybrid system, in vitro binding assay, immunofluorescence localization, stable cell line overexpression with morphological readout The Journal of cell biology High 9885244
1999 The third SH3 domain of vinexin binds Sos (a guanine nucleotide exchange factor for Ras and Rac) both in vitro and in vivo. Growth factor stimulation (EGF, PDGF, serum) causes Sos phosphorylation that disrupts the vinexin-Sos complex. Exogenous vinexin β enhances JNK/SAPK activation but not ERK activation in response to EGF; a point mutation in the third SH3 domain abolishes EGF-induced JNK/SAPK activation in a dominant-negative manner. In vitro binding assay, co-immunoprecipitation, phosphatase treatment, dominant-negative mutant expression, JNK/SAPK kinase activation assay The Journal of biological chemistry High 10585480
2002 Vinexin β expression enables anchorage-independent ERK2 activation stimulated by EGF. The linker region between the second and third SH3 domains of vinexin β (not the SH3 domains themselves) is required for this function. This activity operates through a PKA-PAK signaling pathway: dominant-negative PAK suppresses vinexin β-induced anchorage-independent ERK2 activation, and dominant-negative vinexin β inhibits PKA inhibitor-induced anchorage-independent ERK2 activation. Deletion mutant analysis, dominant-negative constructs, pharmacological inhibitors (H89), ERK2 activation assay in suspended vs. adherent cells The Journal of biological chemistry Medium 11825889
2003 Vinexin α interacts in vitro with estrogen receptor α (ERα), ERβ, androgen receptor, and glucocorticoid receptor; the SH3 domains are not required for this interaction. Co-expression of vinexin α with ERα leads to loss of ERα serine phosphorylation and partial redistribution of vinexin α into the nucleus where it co-localizes with ERα. Vinexin α stimulates ligand-induced transactivation of these receptors. In vitro binding assay, co-immunoprecipitation, immunofluorescence localization, transcriptional reporter assays The Journal of biological chemistry Medium 14625289
2003 Vinexin binds lp-dlg/KIAA0583 (a MAGUK family protein) via the third SH3 domain of vinexin interacting with a proline-rich sequence between the second and third PDZ domains of lp-dlg. lp-dlg co-localizes with vinexin at cell-cell contacts in epithelial cells, co-immunoprecipitates with β-catenin, and the three proteins can form a ternary complex, linking the vinexin-vinculin complex to β-catenin at adherens junctions. Yeast two-hybrid screening, co-immunoprecipitation with deletion mutants, immunofluorescence co-localization The Journal of biological chemistry Medium 12657639
2004 ERK1/2 directly phosphorylates vinexin upon growth factor stimulation. ERK2 phosphorylates serine 189 (in the linker region between the second and third SH3 domains) of vinexin β. Vinexin interacts with the active (but not inactive) form of ERK1/2 via a DEF (FXFP) docking domain in its linker region. Cell adhesion to fibronectin also induces vinexin-ERK2 association and vinexin phosphorylation; vinexin and ERK co-localize at the cell periphery during spreading. In vitro kinase assay, site-directed mutagenesis (Ser189), co-immunoprecipitation, immunofluorescence The Journal of biological chemistry High 15184391
2004 SOCS-7 interacts with vinexin through proline-rich regions N-terminal to the SOCS-7 SH2 domain (likely binding an SH3 domain of vinexin). Vinexin-α co-precipitates with SOCS-7, and part of SOCS-7-GFP merges with vinexin and actin by confocal microscopy, linking SOCS-7 to the actin cytoskeleton via vinexin. Yeast two-hybrid screen, co-immunoprecipitation, confocal immunofluorescence Experimental cell research Medium 15242778
2005 Vinexin β interacts with the non-phosphorylated AF-1 domain of RARγ (identified by yeast two-hybrid). Vinexin β co-localizes with RARγ in the nucleus. Phosphorylation of the AF-1 domain of RARγ prevents vinexin β binding. Stable overexpression of vinexin β or vinexin knockdown by RNAi demonstrates that vinexin β is an inhibitor of RARγ-mediated transcription. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, stable overexpression, siRNA knockdown, transcriptional reporter assays in F9 cells The Journal of biological chemistry High 15734736
2005 SHIP2 interacts with vinexin via its C-terminal region (identified by yeast two-hybrid). The interaction was confirmed by co-immunoprecipitation in COS-7 cells and mouse embryonic fibroblasts. Vinexin α and SHIP2 co-localize at the cell periphery. Vinexin does not affect SHIP2 phosphatase activity in vitro. Co-expression of SHIP2 and vinexin enhances cell adhesion to collagen-I; this requires the SHIP2 C-terminus and catalytic activity. Yeast two-hybrid, co-immunoprecipitation, in vitro phosphatase assay, cell adhesion assay with SHIP2 mutants and knockout MEFs The FEBS journal Medium 16302969
2006 Vinexin β regulates EGFR phosphorylation by suppressing EGFR dephosphorylation (sustaining phosphorylation), requiring both the first and third SH3 domains. Vinexin β binds E3 ubiquitin ligase c-Cbl through its third SH3 domain, decreases the cytosolic pool of c-Cbl and increases membrane-associated c-Cbl; overexpression of c-Cbl abolishes the vinexin β-mediated sustained EGFR phosphorylation. Western blot with phospho-specific antibodies, mutational analysis, siRNA knockdown, co-immunoprecipitation, subcellular fractionation Genes to cells Medium 16923119
2006 Vinexin β interacts with WAVE2 (and also WAVE1 and N-WASP) through its first and second SH3 domains binding the proline-rich region of WAVE2. Vinexin β increases the amount of WAVE2 protein and induces a phosphorylation-dependent mobility shift. This effect requires PKA activity (PKA inhibition suppresses it; PKA activation mimics it) and involves proteasome-dependent regulation of WAVE2 degradation. Co-immunoprecipitation, deletion/point mutant analysis, proteasome inhibitor treatment, PKA pharmacological modulation, SDS-PAGE mobility shift assay Genes to cells Medium 16483316
2006 Abl kinase interacts with vinexin α and β primarily through the third SH3 domain; both co-localize at membrane ruffles in rat astrocytes and the interaction is reduced by the F-actin disruptor latrunculin B (indicating F-actin-mediated regulation). c-Abl and v-Abl phosphorylate vinexin α (but not β) at tyrosine 127, identified by mutational analysis. Co-immunoprecipitation, immunofluorescence, latrunculin B treatment, in vivo phosphorylation assay, site-directed mutagenesis FEBS letters Medium 16831423
2007 ERK-mediated phosphorylation of vinexin β at Ser189 is spatiotemporally regulated: phosphorylated vinexin β is enriched at the leading edge of migrating cells and at the cell periphery during spreading but not at focal adhesions of well-spread cells. Using phosphomimetic and non-phosphorylatable Ser189 mutants, phosphorylation of vinexin β inhibits cell spreading and migration, while unphosphorylated vinexin β inhibits anchorage-independent cell growth. Phosphorylation-state-specific antibody immunofluorescence, stable cell lines expressing GFP-vinexin β phosphomimetic/non-phosphorylatable mutants, cell spreading, migration, and soft-agar growth assays Oncogene Medium 17486060
2007 Vinexin isoforms are expressed in rat brain in a developmental stage-dependent manner; vinexin α is enriched in adult telencephalon. In primary rat hippocampal neurons, vinexin localizes at synapses and filopodia in growth cones (confirmed by biochemical fractionation and electron microscopy). ERK-mediated phosphorylation of vinexin at Ser593 (equivalent to Ser189 in β) occurs at postsynaptic sites of hippocampal synapses (immunoelectron microscopy) and is reduced by the MEK inhibitor PD98059. Immunofluorescence, biochemical fractionation (synaptosomes), electron microscopy, immunoelectron microscopy, phospho-specific antibody, MEK inhibitor Journal of neurochemistry Medium 17241162
2009 Vinexin binds Rhotekin via the C-terminal proline-rich motif of Rhotekin and the third SH3 domain of vinexin. This interaction is little affected by RhoA but is inhibited by activated Cdc42. Vinexin α and Rhotekin partially co-localize at focal adhesions in fibroblasts. Yeast two-hybrid screening, in vitro binding assay, co-immunoprecipitation from COS7 cells and brain tissue, immunofluorescence Medical molecular morphology Medium 19294487
2009 In v-Src-transformed cells, vinexin α is tyrosine phosphorylated at three tyrosine residues. A non-phosphorylatable triple mutant of vinexin α shows higher binding affinity for vinculin than wild-type, demonstrating that tyrosine phosphorylation of vinexin α attenuates its interaction with vinculin. Site-directed mutagenesis, co-immunoprecipitation, binding affinity comparison between wild-type and phosphorylation mutants Biochemical and biophysical research communications Medium 19580787
2010 Vinexin is required for keratinocyte migration and cutaneous wound healing. Vinexin knockdown delays migration of HaCaT and A431 cells in scratch assay without affecting proliferation. Scratch-induced cell migration activates EGFR and ERK; vinexin knockdown inhibits scratch-induced EGFR activation (but not ERK activation), placing vinexin upstream of EGFR in the migration pathway. Vinexin-knockout mice show delayed cutaneous wound healing in vivo. siRNA knockdown, scratch migration assay, pharmacological inhibition (AG1478, U0126), knockout mouse model, in vivo wound healing assay, Western blot for EGFR/ERK activation Experimental cell research High 20361963
2013 Vinexin β protects against cardiac hypertrophy by blocking AKT signaling. Vinexin β overexpression in the heart attenuates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction, while vinexin β knockout exaggerates these responses. Both in vitro and in vivo analyses show that vinexin β's protective effects are associated with AKT signaling abrogation. Transgenic overexpression, knockout mouse model, aortic banding (pressure overload), echocardiography, molecular signaling analysis (AKT phosphorylation), histopathology Basic research in cardiology High 23429936
2014 The proline-rich linker (PRL) region of vinculin and its binding protein vinexin α are required for sensing ECM stiffness. On rigid substrates, vinculin more stably localizes to focal adhesions; mutations in the PRL region or depletion of vinexin impair this stiffness response. Vinexin depletion also impairs stiffness-dependent regulation of cell migration. Vinexin siRNA knockdown, vinculin PRL mutants, FRAP (fluorescence recovery after photobleaching) at focal adhesions, cell migration assays on substrates of varying stiffness Journal of cell science High 24554436
2014 Vinexin (CPEB4-interacting protein) is a novel component of stress granules (SGs). Under arsenite-induced stress, vinexin translocates from focal adhesions to SGs; this translocation depends on its interaction with CPEB4. JNK signaling activated by arsenite enhances the CPEB4-vinexin association and promotes SG localization of vinexin. Vinexin localization to SGs influences SG formation and cell survival. Co-immunoprecipitation, immunofluorescence (FA-to-SG translocation), JNK signaling pharmacological inhibition, siRNA knockdown, cell survival assay PloS one Medium 25237887
2015 Vinexin β binds HCV NS5A via conserved Pro-X-X-Pro-X-Arg motifs at the NS5A C-terminus and the third SH3 domain of vinexin β (residues W307 and Y325 are indispensable). Vinexin β modulates NS5A hyperphosphorylation in a casein kinase 1α-dependent manner; knockdown of vinexin β suppresses NS5A hyperphosphorylation and decreases HCV replication, which is rescued by shRNA-resistant vinexin β. Co-immunoprecipitation (endogenous and exogenous), site-directed mutagenesis (W307, Y325 in SH3; PxxPxR in NS5A), siRNA/shRNA knockdown, HCV replication assay, rescue experiment Journal of virology High 25972535
2016 SORBS3 (vinexin) co-activates estrogen receptor α (ERα) signaling, which indirectly represses STAT3 signaling in hepatocellular carcinoma cells. SORBS3 overexpression leads to decreased IL-6 target gene expression and reduced STAT3 signaling. SORBS3 and SH2D4A cooperate to inhibit HCC cell growth and clonogenicity more than either alone. Gene overexpression in HCC cells, gene expression profiling, STAT3 signaling assays, cell growth and clonogenicity assays, in situ and in vitro co-immunoprecipitation Hepatology Medium 27311882
2017 Vinexin α and CAP (another SORBS family member) co-localize with vinculin at focal adhesions and promote vinculin-rich FAs and ECM stiffness-dependent vinculin behavior, whereas ArgBP2 co-localizes with α-actinin at proximal FA ends and on actin stress fibers, stabilizes α-actinin, and enhances intracellular contractile forces. These results define distinct mechanosensing roles of vinexin α vs. ArgBP2 within the SORBS family. Reconstituted MEF cell lines expressing individual SORBS proteins, immunofluorescence, traction force microscopy, FA morphometry Journal of cell science Medium 28864765
2017 Vinexin localizes to the midbody during cell division and recruits Rhotekin to the midbody via a rhotekin-binding motif; this is required for cytokinetic abscission. Knockdown of vinexin or overexpression of a vinexin mutant lacking the rhotekin-binding motif impairs cytokinetic abscission and increases cells arrested at the midbody stage. Immunofluorescence localization during cell division, siRNA knockdown, mutant overexpression, time-lapse imaging of cytokinesis Cell cycle Medium 28118077
2018 Vinexin α and CAP are necessary for association of vinculin with the cytoskeleton and for YAP/TAZ nuclear localization in mesenchymal stem cells (MSCs) grown on rigid substrates. CAP regulates stiffness-dependent MSC differentiation, while vinexin depletion suppresses adipocyte differentiation independently of YAP/TAZ. siRNA knockdown, rigid/soft substrate culture, immunofluorescence of vinculin-cytoskeleton association, YAP/TAZ nuclear/cytoplasmic fractionation, MSC differentiation assays Scientific reports Medium 30068914
2019 An amphipathic helix (H2) in vinexin α constitutes a novel vinculin-binding site, interacting with the vinculin D1b subdomain and promoting formation of a talin-vinculin-vinexin α ternary complex. H2 mutations impair the ability of vinexin α to induce an ECM stiffness-dependent 'open' conformational change in vinculin and to promote nuclear localization of YAP/TAZ on rigid ECM. Mutagenesis of H2 helix, co-immunoprecipitation, in vitro binding assays, FRET-based vinculin conformation assay, YAP/TAZ nuclear localization assay on substrates of varying stiffness Journal of cell science High 30578314
2021 SORBS3/vinexin is a negative regulator of autophagy. SORBS3 knockdown increases F-actin structures, which compete with YAP/TAZ for binding to angiomotins (AMOTs) in the cytosol, freeing YAP/TAZ to translocate to the nucleus and increase transcriptional activity, thereby upregulating autophagosome biogenesis. Increased SORBS3 expression in aging mouse and human brains correlates with autophagic decline. siRNA knockdown, autophagy flux assays, F-actin imaging, YAP/TAZ nuclear/cytoplasmic localization assay, co-immunoprecipitation (YAP/TAZ-AMOT), gene expression analysis in aged brain tissue Cell death and differentiation Medium 34848853
2022 SORBS3 depletion upregulates YAP1-WWTR1/TAZ target gene expression (including myosin- and actin-related genes) by releasing YAP/TAZ from AMOT-mediated cytosolic retention via increased F-actin structures, thereby promoting autophagosome formation. YAP1-WWTR1/TAZ target genes are downregulated in older mouse and human brains alongside increased SORBS3 expression. siRNA knockdown, YAP/TAZ nuclear translocation assay, target gene expression (RNA-seq/qPCR), autophagy flux assay, brain tissue gene expression analysis Autophagy Medium 35822241
2024 UBE2T mediates ubiquitination and proteasomal degradation of SORBS3 in lung adenocarcinoma cells. Co-immunoprecipitation and ubiquitination assays demonstrate direct interaction between UBE2T and SORBS3. UBE2T-mediated SORBS3 degradation enhances IL-6/STAT3 signaling; restoration of SORBS3 suppresses this signaling and inhibits LUAD progression in vitro and in xenograft models. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, overexpression, in vitro cell function assays (proliferation, migration, invasion, apoptosis), xenograft mouse model Journal of biochemical and molecular toxicology Medium 38816989
2025 SORBS3-β (vinexin β isoform) directly binds β-catenin and recruits UBA1 to enhance ubiquitination and proteasomal degradation of β-catenin, thereby inhibiting Wnt/β-catenin signaling. Downstream, this reduces VEGFC expression and suppresses lymphangiogenesis. In vivo, SORBS3-β overexpression attenuates lymphatic metastasis in cervical cancer xenograft models. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, lentiviral overexpression, Transwell invasion/migration assay, lymphangiogenesis assay, in vivo footpad xenograft model, LC-MS/MS, RNA-seq Journal of translational medicine Medium 40200335
2013 In zebrafish, Sorbs3 (ouchless mutant) is required for dorsal root ganglion (DRG) neurogenesis. Sorbs3 interacts genetically with erbb3 (ErbB receptor) in DRG development, and Sorbs3 is proposed to integrate ErbB signals through MAPK to upregulate neurogenin1. MEK inhibitors phenocopy the ouchless DRG defect. Zebrafish forward genetic screen (ouchless mutant), genetic epistasis with erbb3 allele, pharmacological MEK inhibition, in situ hybridization Development Medium 24004948
2023 In C. elegans, SORB-1/vinexin interacts with RTKN-1/Rhotekin and DEB-1/vinculin in a complex that promotes axon regeneration. RTKN-1 links the DEB-1-SORB-1 complex to ALP-1 (which scaffolds phosphorylated myosin light chain), physically connecting MLC phosphorylation to the actin cytoskeleton during axon regeneration. Genetic epistasis in C. elegans, co-immunoprecipitation, in vivo axon regeneration assay PLoS genetics Medium 38150455

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction. Cell structure and function 180 11937713
1999 Vinexin: a novel vinculin-binding protein with multiple SH3 domains enhances actin cytoskeletal organization. The Journal of cell biology 162 9885244
1999 nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP). The Journal of biological chemistry 73 10521485
2003 Interaction of lp-dlg/KIAA0583, a membrane-associated guanylate kinase family protein, with vinexin and beta-catenin at sites of cell-cell contact. The Journal of biological chemistry 60 12657639
2005 SHIP2 interaction with the cytoskeletal protein Vinexin. The FEBS journal 53 16302969
2014 The role of the interaction of the vinculin proline-rich linker region with vinexin α in sensing the stiffness of the extracellular matrix. Journal of cell science 46 24554436
2005 Vinexin beta interacts with the non-phosphorylated AF-1 domain of retinoid receptor gamma (RARgamma) and represses RARgamma-mediated transcription. The Journal of biological chemistry 45 15734736
1999 Vinexin forms a signaling complex with Sos and modulates epidermal growth factor-induced c-Jun N-terminal kinase/stress-activated protein kinase activities. The Journal of biological chemistry 44 10585480
2004 Extracellular signal-regulated kinase activated by epidermal growth factor and cell adhesion interacts with and phosphorylates vinexin. The Journal of biological chemistry 43 15184391
2017 Vinexin family (SORBS) proteins play different roles in stiffness-sensing and contractile force generation. Journal of cell science 35 28864765
2002 Vinexin beta regulates the anchorage dependence of ERK2 activation stimulated by epidermal growth factor. The Journal of biological chemistry 34 11825889
2016 Chromosome 8p tumor suppressor genes SH2D4A and SORBS3 cooperate to inhibit interleukin-6 signaling in hepatocellular carcinoma. Hepatology (Baltimore, Md.) 32 27311882
2013 Vinexin-β protects against cardiac hypertrophy by blocking the Akt-dependent signalling pathway. Basic research in cardiology 32 23429936
2009 Interaction of a multi-domain adaptor protein, vinexin, with a Rho-effector, Rhotekin. Medical molecular morphology 28 19294487
2004 The suppressor of cytokine signaling (SOCS)-7 interacts with the actin cytoskeleton through vinexin. Experimental cell research 28 15242778
2010 Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo. Experimental cell research 27 20361963
2006 Protein kinase A-dependent increase in WAVE2 expression induced by the focal adhesion protein vinexin. Genes to cells : devoted to molecular & cellular mechanisms 26 16483316
2007 Essential roles of ERK-mediated phosphorylation of vinexin in cell spreading, migration and anchorage-independent growth. Oncogene 21 17486060
2021 Vinexin contributes to autophagic decline in brain ageing across species. Cell death and differentiation 20 34848853
2007 Phosphorylation by extracellular signal-regulated kinase of a multidomain adaptor protein, vinexin, at synapses. Journal of neurochemistry 20 17241162
2003 The focal adhesion protein vinexin alpha regulates the phosphorylation and activity of estrogen receptor alpha. The Journal of biological chemistry 20 14625289
2017 Alterations of sorbin and SH3 domain containing 3 (SORBS3) in human skeletal muscle following Roux-en-Y gastric bypass surgery. Clinical epigenetics 19 28883895
2006 Abl kinase interacts with and phosphorylates vinexin. FEBS letters 19 16831423
2018 Vinexin family (SORBS) proteins regulate mechanotransduction in mesenchymal stem cells. Scientific reports 17 30068914
2014 Arsenite-activated JNK signaling enhances CPEB4-Vinexin interaction to facilitate stress granule assembly and cell survival. PloS one 17 25237887
2001 Expression of vinexin alpha in the dorsal half of the eye and in the cardiac outflow tract and atrioventricular canal. Mechanisms of development 16 11472845
2006 Vinexin beta regulates the phosphorylation of epidermal growth factor receptor on the cell surface. Genes to cells : devoted to molecular & cellular mechanisms 15 16923119
2017 Vinexin β Ablation Inhibits Atherosclerosis in Apolipoprotein E-Deficient Mice by Inactivating the Akt-Nuclear Factor κB Inflammatory Axis. Journal of the American Heart Association 13 28209562
2019 An amphipathic helix of vinexin α is necessary for a substrate stiffness-dependent conformational change in vinculin. Journal of cell science 12 30578314
2013 Modulation of dorsal root ganglion development by ErbB signaling and the scaffold protein Sorbs3. Development (Cambridge, England) 12 24004948
2010 Site-specific protein backbone and side-chain NMR chemical shift and relaxation analysis of human vinexin SH3 domain using a genetically encoded 15N/19F-labeled unnatural amino acid. Biochemical and biophysical research communications 12 20946873
2007 Changes in vinexin expression patterns in the mouse testis induced by developmental exposure to 17beta-estradiol. Biology of reproduction 10 17582013
2024 UBE2T mediates SORBS3 ubiquitination to enhance IL-6/STAT3 signaling and promote lung adenocarcinoma progression. Journal of biochemical and molecular toxicology 8 38816989
2022 Increased SORBS3 expression in brain ageing contributes to autophagic decline via YAP1-WWTR1/TAZ signaling. Autophagy 8 35822241
2015 Vinexin-β exacerbates cardiac dysfunction post-myocardial infarction via mediating apoptotic and inflammatory responses. Clinical science (London, England : 1979) 8 25658191
2015 Vinexin β Interacts with Hepatitis C Virus NS5A, Modulating Its Hyperphosphorylation To Regulate Viral Propagation. Journal of virology 7 25972535
2009 v-Src-mediated transformation suppresses the expression of focal adhesion protein vinexin. Cancer letters 7 19217206
2015 Vinexin-β deficiency protects against cerebral ischaemia/reperfusion injury by inhibiting neuronal apoptosis. Journal of neurochemistry 6 25824575
2013 Localization of multidomain adaptor proteins, p140Cap and vinexin, in the pancreatic islet of a spontaneous diabetes mellitus model, Otsuka Long-Evans Tokushima Fatty rats. Medical molecular morphology 5 23325552
2009 Tyrosine phosphorylation of vinexin in v-Src-transformed cells attenuates the affinity for vinculin. Biochemical and biophysical research communications 5 19580787
2017 Midbody localization of vinexin recruits rhotekin to facilitate cytokinetic abscission. Cell cycle (Georgetown, Tex.) 4 28118077
2025 Oncogenic RARγ isoforms promote head and neck cancer proliferation through vinexin-β-mediated cell cycle acceleration and autocrine activation of EGFR signal. International journal of biological sciences 3 39744424
2025 SORBS3-β suppresses lymph node metastasis in cervical cancer by promoting the ubiquitination of β-catenin. Journal of translational medicine 3 40200335
2022 Vinexin β deficiency exacerbates diet-induced obesity, hepatosteatosis, insulin resistance and endoplasmic reticulum stress in mice. Biochemical and biophysical research communications 1 35104662
2025 LILRB1 enhances the progression of diffuse large B-cell lymphoma through the CREB-SORBS3 pathway. Cellular oncology (Dordrecht, Netherlands) 0 40332648
2023 Rhotekin regulates axon regeneration through the talin-Vinculin-Vinexin axis in Caenorhabditis elegans. PLoS genetics 0 38150455

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