Affinage

RHOA

Transforming protein RhoA · UniProt P61586

Round 2 corrected
Length
193 aa
Mass
21.8 kDa
Annotated
2026-04-28
130 papers in source corpus 53 papers cited in narrative 51 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RhoA is a small GTPase molecular switch that cycles between GTP-bound active and GDP-bound inactive states to coordinate actin cytoskeletal organization, actomyosin contractility, cell migration, mechanotransduction, and cell fate decisions across virtually all mammalian cell types. In its GTP-bound form, RhoA directly activates ROCK (stimulating the LIMK→cofilin and myosin phosphatase axes to drive stress fiber formation and contractility), mDia formins (promoting actin polymerization through profilin), and MEKK1 (engaging the JNK cascade); its spatiotemporal activity is tuned by numerous GEFs (mNET1, PDZ-RhoGEF, GEF-H1, p114-RhoGEF, Daam1), GAPs (p190RhoGAP, ARHGAP29), RhoGDIα-mediated cytosolic sequestration, ubiquitin-dependent degradation (Smurf1 opposed by synaptopodin; KCTD13/CUL3), and direct inhibitory binding by p27Kip1, p120 catenin, and Fam65b (PMID:8617235, PMID:9214622, PMID:14581471, PMID:10436159, PMID:16622418, PMID:29088697, PMID:15078817, PMID:10980705). RhoA-dependent mechanosensing operates through integrin, cadherin, JAM-A, and syndecan-4 receptor systems that engage specific GEFs to translate extracellular tension into cortical stiffness and junction remodeling, while pulsatile RhoA activation—amplified by anillin's kinetic scaffolding—drives irreversible epithelial cell shape changes (PMID:30318244, PMID:26985018, PMID:31907416, PMID:31105010, PMID:31883774). The recurrent somatic RHOA Gly17Val mutation, which abolishes GTP binding and sequesters GEF proteins as a dominant-negative, drives angioimmunoblastic T-cell lymphoma (AITL) cooperatively with TET2 loss by promoting aberrant T follicular helper cell differentiation via ICOS/PI3K signaling (PMID:24413737, PMID:24584070, PMID:29398449).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1989 Medium

    Establishing that RhoA overexpression—without activating point mutations analogous to Ras—is sufficient for oncogenic transformation answered whether Rho-family GTPases possess intrinsic transforming capacity.

    Evidence Cotransfection/DHFR amplification of wild-type rhoH12 in NIH 3T3 cells with focus assay, soft agar growth, and nude mouse tumorigenicity

    PMID:2501657

    Open questions at the time
    • Mechanism of transformation unknown at this stage
    • No downstream effector identified
    • Overexpression system may not reflect physiological regulation
  2. 1996 High

    Identification of ROCK as a direct RhoA effector whose kinase activity is stimulated ~10-fold by GTP-RhoA binding established the first defined enzymatic output of the RhoA switch and explained how RhoA controls phosphorylation-dependent cytoskeletal rearrangements.

    Evidence Ligand overlay, in vitro kinase assay, co-IP in COS cells, effector-domain mutagenesis (A37), replicated independently in two labs

    PMID:8617235 PMID:8641286

    Open questions at the time
    • ROCK substrates mediating actin effects not yet identified
    • Contribution of other effectors unknown
  3. 1997 High

    Discovery that mDia (a formin) is a second major RhoA effector that promotes actin polymerization through profilin resolved how RhoA drives de novo filament assembly independently of ROCK-mediated contractility.

    Evidence Affinity purification of p140mDia as GTP-RhoA binding partner, confocal co-localization with profilin, overexpression-induced actin filament formation

    PMID:9214622

    Open questions at the time
    • Relative contributions of ROCK vs mDia to different actin structures unclear
    • Regulatory mechanism of mDia autoinhibition not defined
  4. 1998 High

    Characterization of mNET1 as a RhoA-selective GEF that induces stress fibers and activates SRF and JNK established the principle that upstream GEFs confer pathway specificity to RhoA outputs.

    Evidence DH-domain mutagenesis, SRF-luciferase reporter, kinase assays, C3-transferase sensitivity

    PMID:9670022

    Open questions at the time
    • How GEF selectivity is enforced in vivo not resolved
    • SRF activation mechanism downstream of RhoA not fully elucidated
  5. 1999 High

    Reconstitution of the ROCK→LIMK→cofilin phosphorylation cascade explained how RhoA-ROCK signaling stabilizes actin filaments by inactivating the depolymerizing factor cofilin, completing a linear pathway from GTPase to actin dynamics.

    Evidence Sequential in vitro kinase assays, ROCK inhibitor Y-27632, phospho-cofilin immunoblot in HeLa cells

    PMID:10436159

    Open questions at the time
    • Spatial regulation of cofilin phosphorylation within cells unknown
    • Contribution of other cofilin kinases not excluded
  6. 2000 High

    Demonstration that p120 catenin and p27Kip1 directly inhibit RhoA activation—by interfering with GEF access—revealed that RhoA is controlled not only by canonical GAPs/GDIs but also by non-canonical protein inhibitors coupling cell adhesion and cell-cycle state to cytoskeletal tension.

    Evidence In vitro RhoA activity assays, GST pull-downs, p27-null fibroblast rescue with CDK-binding-defective p27CK-, ROCK inhibitor rescue of migration

    PMID:10980705 PMID:15078817

    Open questions at the time
    • Structural basis for p120 or p27 blocking GEF access not determined
    • In vivo stoichiometry of these interactions unknown
  7. 2001 High

    Linking RhoA to Wnt/Frizzled signaling through Daam1-mediated Dvl–RhoA complex formation and demonstrating RhoA's requirement for leukocyte tail detachment expanded RhoA's role from generic cytoskeletal regulator to a signal integrator in morphogenesis and immune cell migration.

    Evidence Daam1 Co-IP and dominant-negative in Xenopus gastrulation; C3 transferase/ROCK inhibitor in migrating leukocytes with tat-RhoA rescue

    PMID:11452009 PMID:11779461

    Open questions at the time
    • How Daam1-RhoA interaction is terminated unknown
    • Specific GEF activating RhoA at leukocyte uropod not identified
  8. 2001 High

    Live imaging of GFP-RhoA with RhoGDIα co-expression and mutational analysis established that RhoGDIα sequesters RhoA in the cytosol via the C-terminal hypervariable region, and that GEF-mediated activation triggers membrane translocation, defining the spatial regulatory cycle.

    Evidence GFP-RhoA live-cell imaging, RhoGDIα overexpression, Dbl-mediated activation, palmitoylation inhibitor, subcellular fractionation

    PMID:11149925

    Open questions at the time
    • Mechanism by which GEFs extract RhoA from RhoGDI not resolved
    • Post-translational modifications regulating this cycle not fully catalogued
  9. 2003 High

    Demonstration that RhoA activity rises during mitotic rounding (via p190RhoGAP inactivation) and that RhoA binds and activates MEKK1 (10-fold stimulation of JNK cascade) extended RhoA function to mitotic cortical mechanics and MAP kinase signaling beyond the cytoskeletal effector axis.

    Evidence AFM cortical stiffness + GST-Rhotekin pull-down in synchronized cells; GST pull-down and in vitro kinase assay with MEKK1 PHD-domain mutants

    PMID:12538643 PMID:14581471

    Open questions at the time
    • How p190RhoGAP is phosphorylated during mitosis not identified
    • Physiological importance of RhoA-MEKK1 vs other MEKK1 activators unclear
  10. 2004 High

    Showing that cell shape controls mesenchymal stem cell osteogenic vs adipogenic fate through endogenous RhoA/ROCK activity levels established RhoA as a mechanotransduction hub linking physical microenvironment to lineage commitment.

    Evidence Micropatterned substrates, constitutively active/dominant-negative RhoA, ROCK inhibitor, GTP-RhoA pull-down, differentiation markers

    PMID:15068789

    Open questions at the time
    • Transcriptional targets downstream of ROCK in lineage specification not mapped
    • Whether RhoA acts through YAP/TAZ in this context unknown at this time
  11. 2006 High

    Discovery that synaptopodin stabilizes RhoA by competitively blocking Smurf1-mediated ubiquitination and proteasomal degradation revealed a post-translational regulatory layer controlling RhoA protein levels, not just GTP loading.

    Evidence Ubiquitination assays, competitive Co-IP, RNAi in podocytes, constitutively active RhoA rescue of stress fibers

    PMID:16622418

    Open questions at the time
    • Other tissues where synaptopodin-Smurf1 competition operates not defined
    • Whether other E3 ligases besides Smurf1 target RhoA not explored
  12. 2014 High

    Identification of the recurrent somatic RHOA G17V mutation in ~68% of AITL cases—biochemically demonstrated to abolish GTP binding and sequester GEF proteins as a dominant-negative—established RhoA loss-of-function as an oncogenic driver in T-cell lymphoma, cooperating with TET2 mutations.

    Evidence Exome sequencing of AITL tumors, GTP-binding assay, dominant-negative functional assay, replicated across three independent studies

    PMID:24413734 PMID:24413737 PMID:24584070

    Open questions at the time
    • How GEF sequestration promotes lymphomagenesis mechanistically not yet clear
    • Whether other RHOA mutations in lymphoma act by the same mechanism unknown
  13. 2017 High

    Demonstration that KCTD13/CUL3-mediated ubiquitination of RhoA controls synaptic transmission—with Kctd13 deletion elevating RhoA protein and impairing synapses reversibly by RhoA inhibition—provided a second E3 ligase system regulating RhoA levels and linked RhoA dosage to neuronal physiology.

    Evidence Kctd13 knockout mice, electrophysiology, RhoA protein quantification, pharmacological RhoA inhibitor rescue, zebrafish replication

    PMID:29088697

    Open questions at the time
    • Whether KCTD13 targets GTP-RhoA or GDP-RhoA preferentially not determined
    • Downstream RhoA effector in synaptic transmission not identified
  14. 2018 High

    In vivo modeling confirmed that RHOA G17V cooperates with Tet2 loss to drive AITL via Tfh cell specification through ICOS/PI3K/MAPK signaling, and defined the mechanosensitive Myosin VI→Gα12→p114-RhoGEF→RhoA→mDia1 pathway as a junctional integrity guardian, resolving two distinct in vivo functions of RhoA.

    Evidence Retroviral RHOA G17V in Tet2−/− mice with ICOS/PI3K inhibitor rescue; optogenetics and mechanical stress with Co-IP of Myosin VI/E-cadherin/Gα12 complex

    PMID:29398449 PMID:30318244

    Open questions at the time
    • How ICOS upregulation is mechanistically linked to G17V dominant-negative activity not resolved
    • Whether the Myosin VI pathway operates in non-epithelial tissues unknown
  15. 2019 High

    The kinetic scaffolding model—where anillin cyclically rebinds GTP-RhoA to extend its cortical dwell time and concentrate PIP2—and the demonstration that pulsatile RhoA duration dictates reversible vs irreversible junction remodeling provided a biophysical framework for how RhoA signal dynamics encode morphogenetic outcomes.

    Evidence FRAP kinetics with anillin mutants disrupting RhoA/PIP2 binding; optogenetic RhoA activation with variable pulse duration, formin/dynamin inhibitors

    PMID:31105010 PMID:31883774

    Open questions at the time
    • Whether kinetic scaffolding applies at non-cytokinetic cortical sites not tested
    • How pulse duration is physiologically regulated upstream of RhoA unknown
  16. 2023 High

    Cryo-EM resolution of the TRPV4–RhoA complex revealed a direct structural interaction at the channel's ankyrin repeat domain through which RhoA suppresses channel activity, providing the first atomic-level view of RhoA as a direct allosteric modulator of an ion channel.

    Evidence Cryo-EM structure, interface mutagenesis, electrophysiology with TRPV4 agonist/inhibitor

    PMID:37353478

    Open questions at the time
    • Whether RhoA modulates other TRP channels not explored
    • GTP-loading state of RhoA in the resolved complex not definitively assigned
    • Physiological contexts where RhoA-TRPV4 interaction is rate-limiting remain undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how the dozens of RhoA GEFs and GAPs are spatiotemporally coordinated within a single cell to generate distinct local RhoA activity pools, how RhoA signal dynamics (pulse amplitude, duration, frequency) are decoded by effectors to produce discrete morphogenetic outcomes, and whether the dominant-negative RHOA G17V mutation drives lymphomagenesis solely through GEF sequestration or also through gain-of-function effector interactions.
  • No integrative spatial map of GEF/GAP activity gradients in any single cell type
  • Quantitative relationship between RhoA-GTP levels and effector activation thresholds not established
  • Therapeutic targeting of RhoA pathway in AITL lacks clinical validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005856 cytoskeleton 4 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-168256 Immune System 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1500931 Cell-Cell communication 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1640170 Cell Cycle 2
Partners
ANLNARHGDIACDKN1BCTNND1DIAPH1ROCK1ROCK2TRPV4
Complex memberships
TRPV4-RhoA complex

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 Human rhoH12 (RhoA) gene product was characterized as a 21 kDa protein; amplification of normal rhoH12 via cotransfection caused reduced serum dependence, higher saturation density, and tumorigenicity in nude mice, establishing oncogenic potential of RhoA overexpression without classical ras-like point mutations at residues 14 or 64. Transfection/cotransfection with DHFR amplification, focus assays, soft agar growth, nude mouse tumorigenicity, Western blot/immunoprecipitation Molecular and cellular biology Medium 2501657
1996 RhoA (GTP-bound form) directly binds to and activates Rho-associated kinase (ROCK/Rho-kinase, p160/p164), a serine/threonine kinase; binding requires the effector domain of RhoA (abolished by RhoA A37 mutation) and stimulates ROCK kinase activity up to 10-fold; co-expression causes RhoA-dependent recruitment of ROCK to the plasma membrane. Ligand overlay assay, in vitro kinase assay, co-immunoprecipitation in COS cells, dominant-negative/constitutively active mutants, microinjection The EMBO journal / Science High 8617235 8641286
1997 RhoA GTP binds to p140mDia, a mammalian homolog of Drosophila diaphanous (a formin-family protein), which also binds profilin; RhoA, p140mDia, and profilin co-localize at spreading lamellae, membrane ruffles, and phagocytic cups in a Rho-dependent manner; overexpression of p140mDia induces actin filament formation, identifying mDia as a downstream effector mediating Rho-dependent actin polymerization. Affinity purification, Co-IP, microinjection of C3 exoenzyme, overexpression, confocal co-localization The EMBO journal High 9214622
1998 The DH-domain GEF mNET1 selectively activates RhoA (not Rac1 or Cdc42) to induce actin stress fibers and potentiate serum response factor (SRF) activity; activated mNET1 also activates the SAPK/JNK pathway through a C3-transferase-sensitive GTPase, demonstrating that RhoA GEFs can activate additional signaling pathways beyond direct RhoA-GTP accumulation. Transfection with activated/dominant-negative mutants, DH-domain point mutations, SRF luciferase reporter, kinase assays, pharmacological inhibitors The EMBO journal High 9670022
1999 Signaling from Rho to actin cytoskeleton proceeds via ROCK phosphorylating LIM-kinase, which in turn phosphorylates and inactivates the actin-depolymerizing protein cofilin; this cascade mediates Rho-induced neurite retraction and stress fiber formation. In vitro kinase assays, Y-27632 ROCK inhibitor, overexpression of LIM-kinase in HeLa cells, phospho-cofilin western blot Science High 10436159
1999 Diacylglycerol kinase theta (DGKθ) binds specifically to activated (GTP-bound) RhoA but not to inactive RhoA or to Rac/Cdc42; binding requires the RhoA effector loop (abolished by Y34N mutation) and completely inhibits DGKθ catalytic activity, revealing a novel effector relationship where RhoA negatively regulates diacylglycerol metabolism. Co-IP in transfected COS cells and in neuronal N1E-115 cells, in vitro DGK activity assay, effector-loop point mutant (Y34N) The Journal of biological chemistry High 10066731
2000 p120 catenin selectively inhibits RhoA activity in vitro and in vivo; the RhoA inhibition and p120's interaction with cadherins are mutually exclusive, suggesting that p120 regulates RhoA at nascent cell-cell contacts by interfering with GEF-mediated activation. In vitro RhoA activity assay, pull-down, dominant-negative and active mutants, co-IP Nature cell biology High 10980705
2001 Wnt/Frizzled signaling activates RhoA through the cytoplasmic protein Dishevelled (Dvl) and the novel formin-homology protein Daam1; Daam1 binds both Dvl and RhoA and mediates Wnt-induced Dvl-RhoA complex formation; inhibition of Daam1 blocks Wnt/Fz-induced RhoA activation and Xenopus gastrulation without affecting β-catenin signaling. Co-IP, dominant-negative overexpression, morpholino knockdown in Xenopus embryos, GTP-RhoA pull-down assay Cell High 11779461
2001 Activation of RhoA and ROCK is essential for detachment of the rear of migrating leukocytes; inhibition of RhoA (C3 transferase) or ROCK causes leukocyte tail attachment and blocks transendothelial migration; tat-fusion active RhoA in eosinophils rescues rear detachment in the presence of chemoattractant. GST-Rhotekin GTP-RhoA pulldown assay, C3 transferase, Y-27632 ROCK inhibitor, tat-fusion protein delivery, video microscopy, transwell migration Molecular biology of the cell High 11452009
2001 RhoA subcellular localization is regulated by RhoGDIα binding via the hypervariable C-terminal region; RhoA is predominantly cytosolic even when overexpressed in excess of RhoGDIα, but activated by Dbl translocates to lamellipodia; constitutively active or dominant-negative mutations abrogate RhoGDI binding and redirect RhoA to plasma and internal membranes. GFP-fusion live-cell imaging, co-expression with RhoGDIα, Dbl activation, palmitoylation inhibitor, subcellular fractionation The Journal of cell biology High 11149925
2003 RhoA is required for cortical retraction and the mitotic increase in cortical rigidity during mitotic cell rounding; RhoA activity is elevated in rounded preanaphase mitotic cells, coinciding with decreased activity of the RhoA inhibitor p190RhoGAP due to serine/threonine phosphorylation; Rho-kinase mediates these RhoA effects. Dominant-negative/constitutively active RhoA expression, ROCK inhibitor (Y-27632), atomic force microscopy for cortical stiffness, GST-Rhotekin pull-down, phosphospecific antibodies The Journal of cell biology High 12538643
2003 RhoA binds to the amino-terminal regulatory domain (including its PHD domain) of MEKK1 and stimulates MEKK1 kinase activity up to 10-fold toward MEK4; this interaction is prevented by mutation of the essential cysteine in the MEKK1 PHD domain; Rac and Cdc42 do not bind MEKK1, establishing a specific RhoA–MEKK1–JNK pathway. GST pull-down, in vitro kinase assay, site-directed mutagenesis of MEKK1 PHD domain The Journal of biological chemistry High 14581471
2003 RhoA-mediated MLC phosphorylation specifically controls pseudopod retraction during chemotaxis, while ERK/MLCK-mediated MLC phosphorylation controls pseudopod extension; the two pathways act through differential phosphorylation of myosin II light chain at the same regulatory site (Ser-19). C3 transferase RhoA inhibition, ERK/MLCK pharmacological inhibitors, immunostaining for phospho-MLC, live-cell microscopy of pseudopodia The Journal of biological chemistry Medium 12571246
2004 Cell shape regulates human mesenchymal stem cell lineage commitment through endogenous RhoA activity: spread cells (high RhoA activity) undergo osteogenesis, while round cells (low RhoA activity) become adipocytes; constitutively active RhoA drives osteogenesis and dominant-negative RhoA drives adipogenesis; the RhoA effector ROCK and actin-myosin tension are required downstream. Micropatterned substrates controlling cell shape, constitutively active/dominant-negative RhoA expression, ROCK inhibitor (Y-27632), GTP-RhoA pull-down, differentiation marker assays Developmental cell High 15068789
2004 p27Kip1 binds directly to RhoA and inhibits RhoA activation by interfering with GEF-RhoA interactions; p27-null fibroblasts have elevated active RhoA, increased stress fibers and focal adhesions, and defective migration; re-expression of p27 (including CDK-binding-defective p27CK-) rescues migration, and ROCK inhibition rescues migration of p27-/- cells. GST pull-down, Co-IP, GTP-RhoA pull-down assay, ROCK inhibitor Y-27632, re-expression of wild-type and mutant p27, migration assay Genes & development High 15078817
2004 Podocalyxin activates RhoA through NHERF and ezrin, leading to redistribution of actin filaments; full-length PC but not the NHERF-binding mutant increases RhoA activity; ezrin binding was mapped to the juxtamembrane cytoplasmic region of podocalyxin. Stable MDCK cell lines, GTP-RhoA pull-down, immunofluorescence, GST pull-down mapping Journal of the American Society of Nephrology Medium 15339978
2005 RhoA/ROCK signaling suppresses chondrogenesis by repressing Sox9 promoter activity and suppressing cortical actin organization; pharmacological ROCK inhibition increases glycosaminoglycan synthesis and Sox9 expression, while RhoA overexpression has opposite effects; actin cytoskeleton dynamics directly regulate Sox9 mRNA levels. ROCK inhibitor Y-27632, constitutively active RhoA overexpression, Sox9 promoter-luciferase assay, actin-modifying drugs (cytochalasin D, jasplakinolide, colchicine), RT-PCR, alcian blue staining The Journal of biological chemistry High 15665004
2005 RhoA activity must be transiently increased then decreased to allow myoblast fusion into myotubes; constitutively active RhoA (V14) inhibits fusion by inducing M-cadherin degradation via monoubiquitination and promoting its entry into a degradative pathway; ROCK inhibition restores M-cadherin at cell-cell contacts; p120 catenin association with M-cadherin is reduced by active RhoA. Constitutively active RhoA (V14) expression, ROCK inhibitor Y-27632, GTP-RhoA pulldown, immunofluorescence, ubiquitination assays, Western blot Molecular biology of the cell Medium 16291866
2005 RhoA activation is sufficient to stimulate β1 and β2 integrin-mediated adhesion in thymocytes; RhoA function is required for integrin activation in vivo and for Rac1/Rap1A-induced integrin activation; RhoA activity is critical for integrin-dependent thymocyte chemokine-driven migration. Dominant-negative/constitutively active RhoA expression, integrin adhesion assays to VCAM-1/fibronectin, transwell migration to chemokines, in vivo Rho function loss model Journal of immunology Medium 15972668
2005 RhoA regulates B cell receptor (BCR) signaling downstream of PI3K: RhoA activation is required for BCR-dependent PLCγ2-mediated IP3 synthesis and PtdIns-4,5-P2 synthesis, leading to calcium mobilization and cell proliferation; providing exogenous PtdIns-4,5-P2 rescues calcium flux in cells lacking RhoA function. Dominant-negative RhoA, C3 toxin, IP3/Ca2+ flux assay, PIP2 supplementation rescue, proliferation assay Molecular cell Medium 15664190
2006 Synaptopodin induces actin stress fibers by competitively blocking Smurf1-mediated ubiquitination of RhoA, thereby preventing proteasomal degradation of RhoA; synaptopodin gene silencing in kidney podocytes causes loss of stress fibers, aberrant filopodia, and impaired cell migration. RNAi knockdown, ubiquitination assays, co-IP, constitutively active RhoA rescue, actin immunofluorescence, migration assay Nature cell biology High 16622418
2007 The p110δ isoform of PI3K negatively regulates RhoA activity; inactivation of p110δ leads to reduced p190RhoGAP activity and reduced RhoA sequestration by p27, resulting in increased RhoA-GTP; ROCK inhibition restores all signaling and functional defects of p110δ inactivation including Akt phosphorylation and chemotaxis, placing RhoA/ROCK downstream of p110δ PI3K in a feedback loop controlling PTEN. Genetic inactivation of p110δ, GTP-RhoA pull-down, ROCK inhibitor, p27 binding assay, p190RhoGAP activity assay The EMBO journal High 17581634
2007 In bovine spermatozoa, RHOA is part of a GNA13-mediated signaling cascade (GNA13→RHOA→ROCK2→LIMK2→cofilin) regulating actin dynamics; RHOA-interacting proteins identified include proacrosin, angiotensin-converting enzyme, tubulin, aldolase C, and AKAP4; AKAP3 phosphorylation regulates its interaction with PRKAR2 and ROPN1, suggesting AKAP-mediated spatial targeting of RHOA signaling in sperm. Western blot, overlay assay, immunoprecipitation, mass spectrometry, GST pull-down, phosphorylation assays Biology of reproduction Medium 17928627
2008 RhoA-GDP (inactive form) regulates RhoB protein stability through RhoGDIα; silencing RhoA causes upregulation of RhoB by extending its half-life; this is mediated by RhoGDIα becoming available to stabilize RhoB when RhoA is absent; a RhoA mutant (R68E) unable to bind RhoGDIα cannot reverse RhoB upregulation upon RhoA silencing. RNAi knockdown, re-expression of wild-type and R68E mutant RhoA, pulse-chase half-life assay, RhoGDIα knockdown, Western blot The Journal of biological chemistry Medium 18524772
2008 Myosin phosphatase-RhoA interacting protein (M-RIP) directly binds both RhoA and the myosin-binding subunit (MBS) of myosin phosphatase in vitro, scaffolding RhoA to the actomyosin contractile filament; M-RIP silencing prevents LPA-induced MBS phosphorylation and myosin phosphatase inhibition, and causes loss of stress fiber-associated RhoA. In vitro binding assays, siRNA knockdown, immunofluorescence, phospho-MBS Western blot Journal of cellular biochemistry Medium 17661354
2009 PYK2 phosphorylates and activates PDZ-RhoGEF, which couples calcium signaling to RhoA activation; knockdown of PDZ-RhoGEF or PYK2 markedly decreases angiotensin II-induced and Ca2+-ionophore-induced RhoA activation in vascular smooth muscle cells, establishing the Ca2+→PYK2→PDZ-RhoGEF→RhoA pathway. Adenoviral overexpression/knockdown, siRNA, in vitro PDZ-RhoGEF phosphorylation by PYK2, GTP-RhoA pull-down (MYPT1 phosphorylation), Ca2+ ionophore treatment Arteriosclerosis, thrombosis, and vascular biology Medium 19759375
2009 Activated RhoA and its effector ROCK1 are sequestered into stress granules (SGs) during cellular stress; sequestration of activated ROCK1 into SGs prevents ROCK1 from interacting with JIP-3 and activating JNK, thereby protecting cells from apoptosis; only activated forms of RhoA/ROCK1, not inactive forms, are recruited to SGs. Immunofluorescence, Co-IP, stress granule fractionation, JNK activity assay, apoptosis assays, dominant-negative/constitutively active mutants Cellular signalling Medium 20004716
2010 Ibuprofen inhibits RhoA activity in neurons via activation of PPARγ; PPARγ agonists mimic ibuprofen's RhoA-inhibiting effect and promote neurite elongation; siRNA knockdown of PPARγ blocks RhoA suppression by ibuprofen/PPARγ agonists, establishing PPARγ as essential mediator coupling ibuprofen to RhoA inhibition. siRNA knockdown of PPARγ, PPARγ pharmacological agonists/antagonists, GTP-RhoA pull-down, neurite outgrowth assay in primary neurons and PC12/B104 cells The Journal of neuroscience Medium 20089905
2010 PLCδ3 negatively regulates RhoA protein expression during neuronal differentiation; PLCδ3 knockdown prevents reduction of RhoA protein upon differentiation stimuli, maintains high RhoA/ROCK activity, and inhibits neurite outgrowth; this inhibition is rescued by dominant-negative RhoA or ROCK inhibitor Y-27632; constitutively active PLCδ3 promotes RhoA downregulation. RNAi knockdown, constitutively active/dominant-negative mutants, ROCK inhibitor, RT-PCR, Western blot, neurite outgrowth quantification The Journal of biological chemistry Medium 21187285
2011 Citron kinase (CIT-K) acts as an upstream regulator (not a downstream effector) of RhoA during late cytokinesis/abscission; active RhoA and anillin are displaced from the midbody in CIT-K-depleted cells; CIT-K overexpression causes abscission delay reversible by RhoA inactivation; CIT-K physically interacts with anillin, and anillin overexpression-induced delay is RhoA-independent. CIT-K siRNA depletion, GTP-RhoA localization by immunofluorescence, time-lapse microscopy, rescue with RhoA inactivation, Co-IP of CIT-K and anillin Molecular biology of the cell Medium 21849473
2012 Protein kinase D (PKD) phosphorylates rhotekin (a RhoA effector) at Ser-435; phosphomimetic S435E rhotekin increases endogenous active RhoA levels and enhances RhoA anchoring at the plasma membrane, leading to enhanced stress fiber formation; PKD thus regulates RhoA activity and actin organization through rhotekin phosphorylation. In vitro kinase assay, phosphomimetic mutagenesis, Co-IP, immunofluorescence, active RhoA pull-down The Journal of biological chemistry Medium 22228765
2014 Somatic RHOA p.Gly17Val mutation found in 68% of AITL samples does not bind GTP and inhibits wild-type RhoA function, acting as a dominant-negative; all cases with Gly17Val also had TET2 mutations; RHOA Gly17Val was found only in tumor cells (not non-tumor hematopoietic cells), while TET2 mutations were in both. Exome sequencing, Sanger sequencing, GTP-binding assay, dominant-negative functional assay Nature genetics High 24413734 24413737 24584070
2014 RHOA Gly17Val is oncogenic in T cell lymphoma: molecular modeling shows loss of GTPase activity; the mutant interferes with RHOA signaling potentially by sequestering activated GEF proteins, establishing the mutation as a driver in AITL via a dominant-negative/GEF-sequestration mechanism. Exome/transcriptome sequencing, multiple molecular assays (GTPase activity, GEF interaction), molecular modeling and docking simulations, integrated pathway analysis Nature genetics High 24584070
2014 PlexinB2 receptor stimulates RhoA activity in migrating cortical neurons by two mechanisms: (1) competing with p190RhoGAP for binding to Rnd3, blocking Rnd3-mediated RhoA inhibition, and (2) recruiting RhoGEFs to directly stimulate RhoA; this antagonistic interaction between PlexinB2 and Rnd3 determines the level of RhoA activity appropriate for cortical neuron radial migration. Co-IP, pull-down, dominant-negative/constitutively active constructs, in utero electroporation in mouse cortex, GTP-RhoA pull-down assay Nature communications High 24572910
2015 A RhoA-ROCK signaling pathway involving LIMK1, PKD1, slingshot phosphatase, cofilin, and dynamin regulates polarized formation of Golgi outposts (GOPs) in dendrites by controlling tubule fission from the somatic Golgi apparatus. Live-cell imaging, dominant-negative RhoA, pharmacological inhibitors of ROCK/LIMK, dynamin inhibitor, confocal microscopy in hippocampal neurons Current biology Medium 25802147
2015 Angiotensin II activates the RhoA GEF Arhgef1 through tyrosine phosphorylation in human vascular smooth muscle cells and peripheral blood mononuclear cells; siRNA silencing of Arhgef1 inhibits Ang II-induced RhoA-ROCK signaling; renin-angiotensin system activation in normotensive subjects increases RhoA-ROCK signaling and stimulates Arhgef1. siRNA knockdown, Arhgef1 phosphorylation (tyrosine) assay, GTP-RhoA pull-down, in vivo low-salt diet intervention in human subjects Hypertension Medium 25870189
2015 RhoA deficiency in T cells inhibits TH2 differentiation and prevents allergic airway inflammation; RhoA couples glycolysis and IL-4 receptor mRNA expression to TH2 differentiation; ROCK inhibition phenocopies RhoA loss in blocking TH2 differentiation. Conditional RhoA knockout mice (CD2-Cre x RhoA-flox), in vitro TH2 polarization, OVA-induced airway inflammation model, Seahorse metabolic analyzer, intracellular cytokine staining, ROCK inhibitor The Journal of allergy and clinical immunology High 26100081
2016 Tension on JAM-A activates RhoA, leading to increased cell stiffness; activation requires PI3K-mediated activation of GEF-H1 and p115 RhoGEF; GEF-H1 is regulated by FAK/ERK and p115 RhoGEF is regulated by Src family kinases; phosphorylation of JAM-A at Ser-284 is required for RhoA activation in response to tension. Magnetic bead pulling to apply tension, GTP-RhoA pull-down, pharmacological inhibitors of PI3K/FAK/ERK/Src, phosphomimetic JAM-A mutants (S284A), AFM cell stiffness measurement Molecular biology of the cell Medium 26985018
2016 RhoA in intestinal epithelial cells (IECs) is regulated by geranylgeranyltransferase-I (GGTase-I)-mediated prenylation; conditional loss of Rhoa or Pggt1b in IECs causes spontaneous chronic intestinal inflammation with cytoskeleton rearrangement, aberrant cell shedding, and loss of epithelial integrity; therapeutic triggering of RhoA signaling suppresses inflammation in GGTase-I-deficient mice. Conditional knockout mice (Rhoa-/- and Pggt1b-/- in IECs), genome-wide IEC transcriptome, GTP-RhoA activity assay, immunohistochemistry, histological scoring The Journal of clinical investigation High 26752649
2016 A RhoA-ROCK-Rnd3 feedback loop determines local actin reassembly sites during membrane blebbing; Eps8 and ezrin mark foci where local actin reassembly initiates for bleb retraction; Rnd3 provides feedback regulation downstream of ROCK to restrict RhoA-driven actin reassembly. Live-cell imaging, GFP-tagged RhoA biosensors, RNAi, dominant-negative mutants, pharmacological ROCK inhibition Proceedings of the National Academy of Sciences Medium 26976596
2017 Kctd13 deletion in mice increases RhoA protein levels (as KCTD13 is a substrate adaptor for the CUL3 ubiquitin ligase targeting RhoA for degradation) and causes reduced synaptic transmission; pharmacological RhoA inhibition reverses the synaptic transmission deficit, establishing KCTD13/CUL3-mediated RhoA ubiquitination as a regulator of neuronal function. Kctd13 knockout mice, Western blot for RhoA protein levels, electrophysiology (synaptic transmission), RhoA inhibitor rescue, zebrafish kctd13 knockdown Nature High 29088697
2018 RHOA G17V expression in CD4+ T cells in mice induces T follicular helper (Tfh) cell specification, increased proliferation via ICOS upregulation and PI3K/MAPK signaling; combined with Tet2 loss, RHOA G17V drives AITL development in mice; ICOS/PI3K blockade inhibits tumor proliferation in vivo. Retroviral/transgenic RHOA G17V expression in CD4+ T cells, Tet2-/- mouse model, flow cytometry, in vivo tumor model, ICOS/PI3K inhibitor treatment Cancer cell High 29398449
2018 A mechanosensitive RhoA pathway at adherens junctions preserves epithelial integrity under acute tensile stress: Myosin VI senses increased junctional tension, recruits Gα12 to E-cadherin, which signals through p114 RhoGEF to activate RhoA; tension-activated RhoA increases tensile strength at multicellular vertices via mDia1-mediated actin assembly. Optogenetics, mechanical monolayer stress application, Co-IP of Myosin VI/E-cadherin/Gα12, dominant-negative constructs, mDia1 inhibition, traction force microscopy Developmental cell High 30318244
2018 Fam65b is an atypical inhibitor of RhoA that restricts spontaneous RhoA activation in resting T lymphocytes; chemokine stimulation phosphorylates Fam65b, decreasing its affinity for RhoA and promoting its translocation from plasma membrane to cytosol, thereby relieving RhoA inhibition and allowing actin polymerization and T cell migration. Conditional Fam65b-knockout mice, GTP-RhoA pull-down, phosphorylation assays, live-cell imaging, intranodal migration assay, in vitro migration assay Frontiers in immunology Medium 30254631
2019 Pulsatile RhoA activity drives epithelial cell shape changes via mechanosensitive endocytosis; short RhoA pulses produce reversible junction contractions while longer pulses produce irreversible junction length changes; irreversible junction deformation requires formin-mediated E-cadherin clustering and dynamin-dependent endocytosis downstream of RhoA-mediated contractility. Optogenetic RhoA activation, vertex model, dynamin inhibitor (dynasore), formin inhibitor (SMIFH2), live-cell imaging, junction length quantification Developmental cell High 31883774
2019 Anillin directly binds GTP-RhoA and antagonizes its labile membrane association; anillin concentrates PIP2 at the membrane to retain GTP-RhoA after it disengages from anillin; cyclic re-binding of GTP-RhoA to anillin creates a kinetic scaffolding mechanism that repeatedly resets RhoA dissociation kinetics, substantially increasing cortical dwell time and effector recruitment. FRAP, live-cell imaging, anillin mutants disrupting RhoA/PIP2 binding, GTP-RhoA pull-down, cortical contractility assays Developmental cell High 31105010
2019 Hypoxia suppresses myofibroblast differentiation by reducing RhoA activity through hypoxia-inducible upregulation of ARHGAP29 (a RhoGAP); ARHGAP29 modulates MRTF-A signaling and thereby controls αSMA expression, cell contractility, and actin reorganization. Primary fibroblast hypoxia culture, GTP-RhoA pull-down, ARHGAP29 siRNA knockdown, αSMA Western blot/immunofluorescence, MRTF-A reporter assay, contractility assay Journal of cell science Medium 30659117
2020 Syndecan-4-mediated tension activates cell-wide RhoA via a kindlin-2/β1 integrin/RhoA axis in a PI3K-dependent manner; the variable region of syndecan-4's cytoplasmic domain is required for mechanical adaptation, facilitating assembly of a syndecan-4/α-actinin/F-actin scaffold; this pathway also controls YAP activation. Magnetic bead pulling on syndecan-4, Co-IP, FRET biosensor for RhoA activity, PI3K inhibitor, kindlin-2 siRNA, β1 integrin blocking Nature materials High 31907416
2021 RhoA within myofibers controls satellite cell fusion and hypertrophic growth by regulating Erk1/2 activation and expression of ECM remodeling enzymes (Mmp9/Mmp13/Adam8) and macrophage chemoattractants (Ccl3/Cx3cl1), creating a permissive microenvironment for muscle hypertrophy; MMP inhibition and macrophage depletion phenocopy RhoA loss. Conditional RhoA knockout in myofibers, overload-induced hypertrophy model, satellite cell fusion assay, immunofluorescence, Western blot, macrophage depletion, MMP inhibitor iScience Medium 35106464
2023 Cryo-EM structure of human TRPV4 in complex with RhoA reveals that RhoA interacts with the membrane-facing surface of the TRPV4 ankyrin repeat domains; the contact interface includes residues mutated in neuropathies; RhoA suppresses TRPV4 channel activity; agonist (4α-PDD) binding causes pore opening while inhibitor (HC-067047) induces a π-to-α helix transition in the pore-forming S6 helix. Cryo-EM structure determination, mutagenesis of interface residues, electrophysiology (channel activity), TRPV4 agonist/inhibitor functional assays Nature communications High 37353478
2023 RhoA promotes osteoclast development via the Akt-mTOR-NFATc1 signaling pathway; conditional deletion of RhoA in the osteoclast lineage causes severe osteopetrosis due to bone resorption suppression; RhoA deficiency suppresses Akt-mTOR-NFATc1 signaling during osteoclast differentiation; RhoA-deficient osteoclast precursors are protected from OVX-induced bone loss. Conditional RhoA knockout in osteoclast lineage, bone histomorphometry, osteoclast differentiation assays, Western blot for Akt/mTOR/NFATc1, OVX mouse model Molecular medicine Medium 37020186

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 3411 32353859
2004 Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Developmental cell 3119 15068789
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2004 Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nature cell biology 1726 15467718
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1999 Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science (New York, N.Y.) 1329 10436159
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
1996 Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. The EMBO journal 899 8641286
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1996 The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton. Molecular and cellular biology 776 8816443
1996 The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. The EMBO journal 769 8617235
1996 Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell 734 8625410
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1997 p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. The EMBO journal 693 9214622
2012 A census of human soluble protein complexes. Cell 689 22939629
2003 Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nature reviews. Neuroscience 676 12951563
2001 Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell 674 11779461
2015 Gene essentiality and synthetic lethality in haploid human cells. Science (New York, N.Y.) 657 26472760
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2001 Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. The Journal of cell biology 587 11149925
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2005 High-throughput mapping of a dynamic signaling network in mammalian cells. Science (New York, N.Y.) 553 15761153
2014 Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nature genetics 529 24413737
2014 Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nature genetics 515 24413734
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 p27Kip1 modulates cell migration through the regulation of RhoA activation. Genes & development 445 15078817
2000 Inhibition of RhoA by p120 catenin. Nature cell biology 389 10980705
2004 Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility. Experimental cell research 388 15501444
2016 RhoA/Rho-Kinase in the Cardiovascular System. Circulation research 362 26838319
2006 Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling. Nature cell biology 349 16622418
2014 A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nature genetics 317 24584070
2005 RhoA/ROCK signaling regulates Sox9 expression and actin organization during chondrogenesis. The Journal of biological chemistry 249 15665004
2003 RhoA is required for cortical retraction and rigidity during mitotic cell rounding. The Journal of cell biology 248 12538643
2001 Activation of Rhoa and ROCK are essential for detachment of migrating leukocytes. Molecular biology of the cell 210 11452009
2018 RHOA G17V Induces T Follicular Helper Cell Specification and Promotes Lymphomagenesis. Cancer cell 179 29398449
2012 From mechanical force to RhoA activation. Biochemistry 175 22931484
2010 RhoA/Rho-kinase and vascular diseases: what is the link? Cellular and molecular life sciences : CMLS 140 20668910
2013 RhoA, RhoB and RhoC have different roles in cancer cell migration. Journal of microscopy 137 23488932
1989 Characterization and expression of the human rhoH12 gene product. Molecular and cellular biology 113 2501657
2007 The p110delta isoform of PI 3-kinase negatively controls RhoA and PTEN. The EMBO journal 111 17581634
1988 Expression of the ras-related ralA, rho12 and rab genes in adult mouse tissues. Oncogene 111 2457862
2005 RhoA GTPase regulates M-cadherin activity and myoblast fusion. Molecular biology of the cell 110 16291866
2017 Kctd13 deletion reduces synaptic transmission via increased RhoA. Nature 108 29088697
2004 Podocalyxin activates RhoA and induces actin reorganization through NHERF1 and Ezrin in MDCK cells. Journal of the American Society of Nephrology : JASN 107 15339978
2018 A Mechanosensitive RhoA Pathway that Protects Epithelia against Acute Tensile Stress. Developmental cell 105 30318244
2009 RhoA/ROCK1 signaling regulates stress granule formation and apoptosis. Cellular signalling 100 20004716
2011 Citron kinase controls abscission through RhoA and anillin. Molecular biology of the cell 99 21849473
2010 The role of RhoA/Rho kinase pathway in endothelial dysfunction. Journal of cardiovascular disease research 98 21264179
1998 Activation of RhoA and SAPK/JNK signalling pathways by the RhoA-specific exchange factor mNET1. The EMBO journal 98 9670022
2019 Mechanotransduction: from the cell surface to the nucleus via RhoA. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 95 31431179
2005 Rac1/Cdc42 and RhoA GTPases antagonistically regulate chondrocyte proliferation, hypertrophy, and apoptosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 90 15883643
2015 RhoA orchestrates glycolysis for TH2 cell differentiation and allergic airway inflammation. The Journal of allergy and clinical immunology 87 26100081
2017 ASIC1 and ASIC3 contribute to acidity-induced EMT of pancreatic cancer through activating Ca2+/RhoA pathway. Cell death & disease 86 28518134
2016 Rac1 and RhoA: Networks, loops and bistability. Small GTPases 86 27533896
1999 Diacylglycerol kinase theta binds to and is negatively regulated by active RhoA. The Journal of biological chemistry 86 10066731
2014 Regulation of RhoA activity by adhesion molecules and mechanotransduction. Current molecular medicine 85 24467208
2020 Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway. Nature materials 84 31907416
2019 RhoA Mediates Epithelial Cell Shape Changes via Mechanosensitive Endocytosis. Developmental cell 83 31883774
2003 ERK and RhoA differentially regulate pseudopodia growth and retraction during chemotaxis. The Journal of biological chemistry 83 12571246
2022 RhoA Signaling in Neurodegenerative Diseases. Cells 80 35563826
2001 Ca2+-RhoA signaling pathway required for polyamine-dependent intestinal epithelial cell migration. American journal of physiology. Cell physiology 79 11245616
2015 A RhoA Signaling Pathway Regulates Dendritic Golgi Outpost Formation. Current biology : CB 76 25802147
2010 A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 75 20089905
2008 Activated RHOA and peripheral axon regeneration. Experimental neurology 74 18554585
2019 RhoA/ROCK pathway: implication in osteoarthritis and therapeutic targets. American journal of translational research 72 31632513
2015 CMKLR1 and GPR1 mediate chemerin signaling through the RhoA/ROCK pathway. Molecular and cellular endocrinology 70 26363224
2019 Anillin Promotes Cell Contractility by Cyclic Resetting of RhoA Residence Kinetics. Developmental cell 69 31105010
2012 Lysophospholipid receptor activation of RhoA and lipid signaling pathways. Biochimica et biophysica acta 69 22986288
2008 RhoA-GDP regulates RhoB protein stability. Potential involvement of RhoGDIalpha. The Journal of biological chemistry 67 18524772
2003 RhoA binds to the amino terminus of MEKK1 and regulates its kinase activity. The Journal of biological chemistry 67 14581471
2016 Statins improve NASH via inhibition of RhoA and Ras. American journal of physiology. Gastrointestinal and liver physiology 65 27634010
2015 MiR-133b Promotes neurite outgrowth by targeting RhoA expression. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 65 25591767
2011 RhoA can lead the way in tumor cell invasion and metastasis. Frontiers in bioscience (Landmark edition) 61 21196273
2005 RhoA GTPase regulates B cell receptor signaling. Molecular cell 60 15664190
2014 CD44 acts through RhoA to regulate YAP signaling. Cellular signalling 57 25101858
2014 An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration. Nature communications 56 24572910
2009 PYK2/PDZ-RhoGEF links Ca2+ signaling to RhoA. Arteriosclerosis, thrombosis, and vascular biology 56 19759375
2007 Identification and characterization of RHOA-interacting proteins in bovine spermatozoa. Biology of reproduction 56 17928627
2005 Integrin regulation by RhoA in thymocytes. Journal of immunology (Baltimore, Md. : 1950) 56 15972668
2023 Structure of human TRPV4 in complex with GTPase RhoA. Nature communications 55 37353478
2022 A current overview of RhoA, RhoB, and RhoC functions in vascular biology and pathology. Biochemical pharmacology 54 36306821
2008 Targeting by myosin phosphatase-RhoA interacting protein mediates RhoA/ROCK regulation of myosin phosphatase. Journal of cellular biochemistry 53 17661354
2005 Prolonged lesional expression of RhoA and RhoB following spinal cord injury. The Journal of comparative neurology 53 15880494
2001 RhoA/Rho-kinase, vascular changes, and hypertension. Current hypertension reports 53 11276396
2014 mTOR regulate EMT through RhoA and Rac1 pathway in prostate cancer. Molecular carcinogenesis 50 25043657
2005 BCL6 suppresses RhoA activity to alter macrophage morphology and motility. Journal of cell science 46 15860730
2016 A RhoA and Rnd3 cycle regulates actin reassembly during membrane blebbing. Proceedings of the National Academy of Sciences of the United States of America 45 26976596
2010 Revisited and revised: is RhoA always a villain in cardiac pathophysiology? Journal of cardiovascular translational research 44 20559774
2018 Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Gα13/RhoA-mediated Migration. Molecular cancer research : MCR 42 29330286
2018 LncRNA PCGEM1 Induces Ovarian Carcinoma Tumorigenesis and Progression Through RhoA Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 42 29949791
2019 RHOA in Gastric Cancer: Functional Roles and Therapeutic Potential. Frontiers in genetics 41 31156701
2016 Pathophysiological effects of RhoA and Rho-associated kinase on cardiovascular system. Journal of hypertension 40 26556565
2016 Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation. The Journal of clinical investigation 40 26752649
2015 Galectin 3 regulates HCC cell invasion by RhoA and MLCK activation. Laboratory investigation; a journal of technical methods and pathology 39 26146960
2017 RhoA as a target to promote neuronal survival and axon regeneration. Neural regeneration research 37 28553321
2008 G protein-coupled receptors go extracellular: RhoA integrates the integrins. Molecular interventions 37 18829842
2017 Daam1 activates RhoA to regulate Wnt5a‑induced glioblastoma cell invasion. Oncology reports 36 29207169
2016 Silencing Drp1 inhibits glioma cells proliferation and invasion by RHOA/ ROCK1 pathway. Biochemical and biophysical research communications 36 27495873
2016 Tension on JAM-A activates RhoA via GEF-H1 and p115 RhoGEF. Molecular biology of the cell 35 26985018
2010 Phospholipase Cdelta3 regulates RhoA/Rho kinase signaling and neurite outgrowth. The Journal of biological chemistry 35 21187285
2003 Effect of focal cerebral infarctions on lesional RhoA and RhoB expression. Archives of neurology 34 12975290
2017 Loss of RhoA promotes skin tumor formation and invasion by upregulation of RhoB. Oncogene 32 29059167
2014 Genistein induces cytokinesis failure through RhoA delocalization and anaphase chromosome bridging. Journal of cellular biochemistry 32 24453048
2011 Cyclic AMP dysregulates intestinal epithelial cell restitution through PKA and RhoA. Inflammatory bowel diseases 31 21993975
2009 Inhibition of RhoA signaling with increased Bves in trabecular meshwork cells. Investigative ophthalmology & visual science 30 19628742
2017 Regulation of RhoA GTPase and novel target proteins for ROCK. Small GTPases 29 29199510
2011 Ovarian cancer: Stat3, RhoA and IGF-IR as therapeutic targets. Cancer letters 29 22120672
2021 Role of Small GTPase RhoA in DNA Damage Response. Biomolecules 28 33546351
2018 RhoA regulates Schwann cell differentiation through JNK pathway. Experimental neurology 28 29940159
2013 Phosphorylation-mediated regulation of GEFs for RhoA. Cell adhesion & migration 28 24589508
2023 RhoA regulation in space and time. FEBS letters 27 36658753
2014 Arhgap28 is a RhoGAP that inactivates RhoA and downregulates stress fibers. PloS one 27 25211221
2022 TRPV4: A trigger of pathological RhoA activation in neurological disease. BioEssays : news and reviews in molecular, cellular and developmental biology 26 35297520
2015 Angiotensin II activates the RhoA exchange factor Arhgef1 in humans. Hypertension (Dallas, Tex. : 1979) 26 25870189
2009 CCK activates RhoA and Rac1 differentially through Galpha13 and Galphaq in mouse pancreatic acini. American journal of physiology. Cell physiology 26 19940064
2003 Vasoconstriction, RhoA/Rho-kinase and the erectile response. International journal of impotence research 26 14551573
2023 RhoA promotes osteoclastogenesis and regulates bone remodeling through mTOR-NFATc1 signaling. Molecular medicine (Cambridge, Mass.) 25 37020186
2018 Afadin and RhoA control pancreatic endocrine mass via lumen morphogenesis. Genes & development 25 29330353
2012 Protein kinase D regulates RhoA activity via rhotekin phosphorylation. The Journal of biological chemistry 25 22228765
2018 Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration. Frontiers in immunology 24 30254631
2013 The role of RhoA kinase (ROCK) in cell alignment on nanofibers. Acta biomaterialia 24 23587628
2021 RhoA within myofibers controls satellite cell microenvironment to allow hypertrophic growth. iScience 23 35106464
2020 Role of Macrophages and RhoA Pathway in Atherosclerosis. International journal of molecular sciences 22 33379334
2019 Hypoxia suppresses myofibroblast differentiation by changing RhoA activity. Journal of cell science 22 30659117