Affinage

LIMK2

LIM domain kinase 2 · UniProt P53671

Length
638 aa
Mass
72.2 kDa
Annotated
2026-06-10
66 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIMK2 is a serine/threonine kinase, defined by N-terminal LIM motifs, a PDZ domain, and a C-terminal kinase domain, that integrates Rho-family GTPase signaling with actin cytoskeletal dynamics and cell cycle control (PMID:7651734, PMID:8954941). Its canonical output is phosphorylation and inactivation of cofilin downstream of a RhoA/RhoC–ROCK module, stabilizing F-actin to drive cell migration and contractility; this axis is required in vivo for keratinocyte migration during eyelid closure, airway smooth muscle contraction, platelet spreading and thrombus formation, and endothelial responses (PMID:23071748, PMID:34353741, PMID:31926945, PMID:35525325). ROCK1 preferentially activates LIMK2 over LIMK1 in a manner specific to mesenchymal-mode migration, and the pathway is constrained by neurofibromin, whose loss elevates cofilin phosphorylation and motility (PMID:18852895, PMID:16455074, PMID:23082153). LIMK2 activity and nuclear–cytoplasmic shuttling are tuned by upstream phosphorylation: PKC-delta phosphorylates Ser-283 to block nuclear import and relieve suppression of cyclin D1, while Aurora A phosphorylates S283/T494/T505 in a reciprocal positive-feedback loop essential for Aurora-A-driven tumorigenesis (PMID:15923181, PMID:22492986). During mitosis LIMK2 localizes to the spindle and, downstream of RhoA-ROCK, regulates astral microtubule organization and spindle orientation through TPPP independently of cofilin, and supports centrosome clustering via an MST4–NPM1 cascade (PMID:16455074, PMID:22328514, PMID:40775397). As a p53 target, LIMK2 promotes survival after DNA damage (PMID:21079653). Beyond cofilin, LIMK2 directly phosphorylates a set of substrates—TWIST1, PTEN, SPOP, NKX3.1, SRPK1, G3BP1, and MST4—frequently within mutual stabilization/degradation feedback loops, to drive context-dependent oncogenic and EMT signaling in prostate, breast, melanoma, and esophageal cancers (PMID:30716360, PMID:32931887, PMID:33311589, PMID:32859889, PMID:34066036, PMID:36922679, PMID:40775397). A distinct isoform, LIMK2-1, lacks direct cofilin kinase output and instead, when phosphorylated by PKC, acts as a CPI-17-like inhibitor of PP1 and myosin phosphatase to indirectly maintain phospho-cofilin (PMID:30373762, PMID:40806479).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1995 Medium

    Established that LIMK2 is a bona fide serine/threonine kinase, defining its catalytic identity and domain architecture.

    Evidence In vitro kinase assay on MBP from immunoprecipitated LIMK2 with two LIM motifs and a kinase domain

    PMID:7651734

    Open questions at the time
    • No physiological substrate identified
    • Regulation of catalytic activity unknown
  2. 1996 Medium

    Resolved that LIMK2 isoforms differ in domain content and partition between nucleus and cytoplasm, raising the question of compartment-specific functions.

    Evidence Transfection, subcellular fractionation, immunofluorescence, and co-precipitation of isoforms LIMK2a/LIMK2b

    PMID:8954941

    Open questions at the time
    • Identity of 63/58-kDa partner proteins unknown
    • Functional consequence of differential localization not tested
  3. 2005 High

    Defined PKC-delta phosphorylation of Ser-283 as a switch controlling LIMK2 nuclear import and cell cycle progression, linking post-translational control to function.

    Evidence FRAP live imaging, leptomycin B, site-directed mutagenesis, and in vitro kinase assay in endothelial cells

    PMID:15923181

    Open questions at the time
    • Nuclear substrate(s) of LIMK2 not identified
    • Direct mechanism linking shuttling to cyclin D1 unresolved
  4. 2005 Medium

    Placed LIMK2 in a Ras-Rho-ROCK pathway constrained by neurofibromin, showing its cofilin-phosphorylating activity drives stress fiber formation and motility.

    Evidence siRNA knockdown, phospho-cofilin Western blot, and NF1-GRD rescue epistasis

    PMID:16169856

    Open questions at the time
    • Direct vs indirect NF1 effect not distinguished here
    • Contribution relative to ROCK-cofilin baseline not quantified
  5. 2006 Medium

    Connected LIMK2 to mitosis, showing spindle/midzone localization and activation upon mitotic arrest, distinct from LIMK1.

    Evidence Cell synchronization, in vitro kinase assay, and immunofluorescence

    PMID:16455074

    Open questions at the time
    • Trigger for mitotic hyperphosphorylation undefined here
    • Mitotic substrate identity not resolved
  6. 2008 Medium

    Demonstrated ROCK1 preferentially activates LIMK2 in a migration-mode-specific manner, refining which migratory programs use this kinase.

    Evidence FRET live-cell imaging of direct interaction and substrate phosphorylation in polarized vs blebbing cells

    PMID:18852895

    Open questions at the time
    • Structural basis of ROCK1 preference for LIMK2 unknown
    • In vivo relevance of mode specificity untested
  7. 2010 Medium

    Identified LIMK2 as a p53 transcriptional target mediating survival after DNA damage, expanding its role beyond cytoskeletal control.

    Evidence siRNA, pharmacological LIMK inhibition, p53 target validation, and viability assays

    PMID:21079653

    Open questions at the time
    • Downstream survival effector of LIMK2 not defined
    • Whether survival is cofilin-dependent unclear
  8. 2012 High

    Revealed reciprocal Aurora A–LIMK2 phosphorylation and a positive-feedback loop required for Aurora-A-driven tumorigenesis, establishing LIMK2 as a mitotic oncogenic node.

    Evidence Analog-sensitive Aurora A chemical genetics, in vitro kinase assay, mutagenesis, and xenograft

    PMID:22492986

    Open questions at the time
    • Mechanism by which LIMK2 raises Aurora A levels unresolved
    • Relative contribution of each phosphosite not dissected
  9. 2012 Medium

    Established a cofilin-independent mitotic function: LIMK2 regulates astral microtubules and spindle orientation via TPPP downstream of RhoA-ROCK.

    Evidence RNAi epistasis and immunofluorescence of microtubules and spindle orientation

    PMID:22328514

    Open questions at the time
    • Whether LIMK2 directly phosphorylates TPPP not shown
    • Coupling to actin-based mitotic roles unclear
  10. 2012 Medium

    Showed NF1 SecPH domain physically binds and inhibits LIMK2 by blocking ROCK activation, providing a direct molecular link between Ras and Rho/ROCK/LIMK2 signaling.

    Evidence Yeast two-hybrid, co-IP, and in vitro kinase inhibition assay

    PMID:23082153

    Open questions at the time
    • Structural interface of NF1-LIMK2 undefined
    • Specificity over LIMK1 mechanism not explained
  11. 2012 High

    Genetically proved the LIMK2-cofilin axis is required in vivo for keratinocyte F-actin nucleation and migration during eyelid development.

    Evidence LIMK2 knockout mouse with F-actin and phospho-cofilin immunofluorescence and eyes-open-at-birth phenotype

    PMID:23071748

    Open questions at the time
    • Redundancy with LIMK1 in other tissues not assessed
    • Upstream activator in keratinocytes not identified
  12. 2013 Medium

    Extended LIMK2 microtubule regulation to drug sensitivity, linking it to microtubule acetylation and TPPP1 in neuroblastoma.

    Evidence siRNA, drug sensitivity and cell cycle assays, Western blot

    PMID:23991158

    Open questions at the time
    • Direct molecular control of acetylation unclear
    • Mechanism distinguishing actin vs microtubule roles undefined
  13. 2013 Medium

    Demonstrated LIMK2 transduces Sema3A chemorepulsion in migrating cortical interneurons, defining a developmental neuronal guidance role.

    Evidence siRNA, chemotactic assays, brain slices, in utero electroporation

    PMID:23519094

    Open questions at the time
    • Receptor-to-LIMK2 signaling steps not mapped
    • Substrate downstream of LIMK2 in interneurons unidentified
  14. 2013 Medium

    Identified a tumor-constraining role: Limk2 deletion enlarges colon tumors and increases GI stem cell proliferation, conserved with Drosophila.

    Evidence Limk2 knockout colitis-associated CRC model and immunostaining

    PMID:23585469

    Open questions at the time
    • Substrate mediating stem-cell restraint unknown
    • Reconciliation with oncogenic roles context-dependence unresolved
  15. 2017 Medium

    Placed LIMK2 downstream of BMPR2 via RhoA/ROCK and as a direct BMPR2 interactor driving osteosarcoma invasion and metastasis.

    Evidence iTRAQ phosphoproteomics, co-IP, and in vitro/in vivo invasion assays

    PMID:28938584

    Open questions at the time
    • Direct LIMK2 substrate in this context not defined
    • BMPR2-LIMK2 binding interface unknown
  16. 2018 High

    Defined the LIMK2-1 isoform as a non-canonical effector that inhibits PP1 toward cofilin rather than phosphorylating cofilin directly.

    Evidence In vitro kinase and PP1 activity assays, co-IP, and stress fiber imaging

    PMID:30373762

    Open questions at the time
    • Kinase function of LIMK2-1, if any, not assigned a substrate
    • Physiological context of isoform expression unclear
  17. 2019 High

    Established the LIMK2-TWIST1 axis: direct phosphorylation stabilizes TWIST1 in a mutual stabilization loop driving EMT and tumor formation in CRPC.

    Evidence Chemical genetic substrate ID, in vitro kinase assay, mutagenesis, ubiquitylation assay, xenograft

    PMID:30716360

    Open questions at the time
    • Phosphosite-level mechanism of degradation protection partial
    • Generality beyond CRPC not tested here
  18. 2019 Medium

    Showed LIMK2 is required in vivo for platelet cytoskeletal function, hemostasis, and thrombus formation.

    Evidence LIMK2a knockout mouse, platelet spreading, aggregation, and thrombus assays

    PMID:31926945

    Open questions at the time
    • Whether effect is solely cofilin-mediated not shown
    • Upstream platelet activator of LIMK2 not defined
  19. 2020 High

    Identified PTEN as a direct LIMK2 substrate, linking hypoxia to PTEN degradation and PI3K/AKT activation in CRPC within a reciprocal degradation loop.

    Evidence In vitro kinase assay, mutagenesis, ubiquitylation, PTEN knockout mouse, xenograft

    PMID:32931887

    Open questions at the time
    • E3 ligase mediating PTEN degradation not identified
    • Phosphosite stoichiometry in vivo unquantified
  20. 2020 High

    Established LIMK2 degrades SPOP by direct phosphorylation, stabilizing AR, ARv7, and c-Myc to drive tumorigenesis.

    Evidence In vitro kinase assay, phospho-resistant SPOP mutagenesis, ubiquitylation assay, xenograft

    PMID:33311589

    Open questions at the time
    • Ligase coupling SPOP phosphorylation to ubiquitylation undefined
    • Crosstalk with other LIMK2 substrates not integrated
  21. 2020 Medium

    Identified SRPK1 as a LIMK2 substrate whose inhibition phenocopies LIMK2 loss in blocking TNBC metastasis.

    Evidence SILAC phosphoproteomics, shRNA, pharmacological inhibition, in vivo metastasis model

    PMID:32859889

    Open questions at the time
    • SRPK1 phosphosite(s) not mapped here
    • Downstream splicing effectors not defined
  22. 2021 Medium

    Added NKX3.1 as a directly phosphorylated, degraded LIMK2 substrate in a reciprocal loop regulating AR and AKT signaling.

    Evidence In vitro kinase assay, co-IP, ubiquitylation assay, xenograft

    PMID:34066036

    Open questions at the time
    • Mechanism of mRNA downregulation unresolved
    • Phosphosites not individually validated functionally
  23. 2021 High

    Demonstrated the LIMK2-cofilin axis is required in vivo for airway smooth muscle contractile force and actin polymerization in a stimulus-specific manner.

    Evidence LIMK2 knockout mouse, force measurements, F/G-actin ratio, phospho-cofilin blot

    PMID:34353741

    Open questions at the time
    • Basis of 5-HT vs acetylcholine specificity unknown
    • Upstream receptor-to-LIMK2 link not mapped
  24. 2021 Medium

    Showed LIMK2 directs definitive endoderm versus neuroectoderm fate in hESCs through cofilin-dependent actin and EMT-gene control.

    Evidence siRNA, F-actin and p-cofilin assays, lineage marker RT-PCR

    PMID:33977398

    Open questions at the time
    • Transcriptional link to fate genes not defined
    • Whether non-cofilin substrates contribute untested
  25. 2022 Medium

    Placed LIMK2 in a Gα13-RhoA/C-ROCK pathway downstream of the TP receptor that restrains endothelial angiogenic sprouting.

    Evidence RNAi, pharmacological inhibition, spheroid sprouting, RhoA/C FRET biosensors

    PMID:35525325

    Open questions at the time
    • Direct LIMK2 substrate in endothelial sprouting not shown
    • Relationship to focal-adhesion regulation mechanistic detail limited
  26. 2023 Medium

    Identified the LIMK2→G3BP1→ESM1 pathway driving melanoma growth and metastasis via mRNA stabilization.

    Evidence Phosphoproteomics, shRNA, RNA-seq, rescue experiments, in vivo tumor models

    PMID:36922679

    Open questions at the time
    • G3BP1 phosphosite and consequence not detailed here
    • How phosphorylation alters ESM1 mRNA stability unclear
  27. 2025 High

    Defined a LIMK2-MST4-NPM1 cascade controlling centrosome clustering, explaining how LIMK2 supports mitotic fidelity in tumor cells.

    Evidence In vitro kinase assay, mutagenesis, co-IP, shRNA, xenograft and 4NQO mouse models

    PMID:40775397

    Open questions at the time
    • Integration with TPPP-based spindle role unresolved
    • Whether MST4 activation occurs in non-cancer mitosis untested
  28. 2025 High

    Characterized LIMK2-1 as a PKC-activated, CPI-17-like inhibitor of PP1c and myosin phosphatase with nanomolar potency, defining a phosphatase-regulatory mode for this isoform.

    Evidence Overexpression, co-IP with PP1c, in vitro phosphatase assay with IC50, phosphospecific antibody

    PMID:40806479

    Open questions at the time
    • Physiological signaling context regulating LIMK2-1 unknown
    • Endogenous expression and abundance not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LIMK2 selects between its canonical cofilin/cytoskeletal output and its diverse non-cytoskeletal substrate program (TWIST1, PTEN, SPOP, NKX3.1, SRPK1, G3BP1, MST4) in a given cell context remains unresolved.
  • No unifying determinant of substrate choice identified
  • Structural basis of substrate recognition undefined
  • Reconciliation of tumor-suppressive and oncogenic roles incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016740 transferase activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 6 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 4
Partners
BMPR2MST4NF1NKX3.1PP1ROCK1SPOPTWIST1

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 LIMK2 is a serine/threonine kinase containing two N-terminal LIM motifs and a C-terminal kinase domain; it phosphorylates serine and threonine residues of myelin basic protein in vitro, demonstrating its catalytic activity. In vitro kinase assay, immunoprecipitation Oncogene Medium 7651734
1996 LIMK2a (two LIM domains + PDZ + kinase) localizes to both cytoplasm and nucleus, while LIMK2b (one and half LIM domains) localizes mainly to cytoplasm; a truncated LIMK2-Kinase construct localizes to the nucleus. LIMK2a and LIMK2b associate with 63-kDa and 58-kDa partner proteins, respectively. Transfection studies, subcellular fractionation, immunofluorescence, co-precipitation Biochemical and biophysical research communications Medium 8954941
1997 Recombinant LIMK2 exhibits autophosphorylation and serine/threonine kinase activity toward exogenous substrate MBP; endogenous LIMK2 co-precipitates with a 140 kDa tyrosine-phosphorylated protein but is not itself tyrosine phosphorylated; LIMK2 localizes in both the nucleus and a Triton X-100 soluble cytoplasmic fraction. In vitro kinase assay, stable transfection, co-precipitation, subcellular fractionation Journal of biochemistry Medium 9089416
2005 PKC-delta phosphorylates LIMK2 at Ser-283 in vitro and in endothelial cells; phosphorylation at Ser-283 (but not Thr-494) inhibits nuclear import of LIMK2, retaining it in the cytoplasm. This cytoplasmic retention is associated with relief of LIMK2-mediated suppression of cyclin D1 expression and promotion of G1-to-S phase transition. EGFP-LIMK2 live imaging, FRAP, leptomycin B treatment, site-directed mutagenesis, in vitro kinase assay, immunofluorescence The Journal of biological chemistry High 15923181
2005 Loss of neurofibromin activates a Rho-ROCK-LIMK2 pathway that elevates cofilin phosphorylation, promoting actin stress fiber formation and enhanced cell motility; this pathway requires Ras activation but is independent of Raf, PI3K, and RalGEF downstream pathways. siRNA knockdown, Western blot for phospho-cofilin, genetic epistasis with NF1-GRD re-expression The Journal of biological chemistry Medium 16169856
2006 LIMK2 activity toward cofilin does not change during normal cell division but is markedly increased when cells are arrested at mitosis by nocodazole-induced microtubule disruption, accompanied by LIMK2 hyperphosphorylation. LIMK2 localizes to the mitotic spindle during prometaphase through anaphase and to the spindle midzone during anaphase–telophase, distinct from LIMK1. Cell synchronization, in vitro kinase assay, immunofluorescence microscopy Experimental cell research Medium 16455074
2008 ROCK1 preferentially phosphorylates LIMK2 over LIMK1; direct ROCK1–LIMK2 interaction detected by FRET occurs in polarized (spread) but not blebbing cancer cells, indicating the ROCK1:LIMK2 pathway is specific to mesenchymal-mode rather than amoeboid-mode migration. FRET live-cell imaging, substrate phosphorylation assays PloS one Medium 18852895
2010 RhoC and LIMK2 are direct transcriptional targets of p53 induced by genotoxic agents; LIMK2 activation downstream of p53 promotes cell survival following DNA damage, and LIMK inhibition sensitizes cells to radio- and chemotherapy. siRNA knockdown, pharmacological inhibition, ChIP/reporter assays (p53 target gene identification), cell viability assays Cell research Medium 21079653
2012 Aurora A kinase directly phosphorylates LIMK2 at S283, T494, and T505, regulating LIMK2 kinase activity, subcellular localization, and protein levels. LIMK2 in turn positively regulates Aurora A levels, forming a positive-feedback loop. LIMK2 ablation fully abrogates Aurora-A-mediated tumorigenesis in vivo. Chemical genetic approach (analog-sensitive Aurora A), in vitro kinase assay, site-directed mutagenesis, xenograft mouse model, Western blot Journal of cell science High 22492986
2012 LIMK2 acts downstream of RhoA-ROCK to regulate astral microtubule organization through TPPP (tubulin polymerization promoting protein), independently of cofilin, during mitosis; this pathway controls spindle orientation in mitotic cells. RNAi knockdown, epistasis analysis, immunofluorescence for microtubules and spindle orientation Journal of cell science Medium 22328514
2012 Nf1 RasGAP SecPH domain physically interacts with LIMK2 (but not LIMK1), partially inhibiting LIMK2 kinase activity toward cofilin by preventing ROCK-mediated activation of LIMK2, thereby connecting Ras and Rho/ROCK/LIMK2/cofilin signaling. Yeast two-hybrid screening, co-immunoprecipitation, in vitro kinase assay PloS one Medium 23082153
2012 In LIMK2 knockout mice, keratinocytes fail to nucleate filamentous actin and remain immobile during eyelid development, resulting in eyes open at birth phenotype; this is associated with markedly reduced phospho-cofilin levels, demonstrating that LIMK2 activity and cofilin phosphorylation are required for keratinocyte migration in vivo. Knockout mouse model, immunofluorescence for F-actin and phospho-cofilin, phenotypic analysis PloS one High 23071748
2013 LIMK2 depletion sensitizes neuroblastoma cells to microtubule-targeted drugs by enhancing cell cycle arrest and apoptosis; LIMK2 modulates microtubule acetylation and levels of TPPP1, suggesting a role in regulating the microtubule network independent of actin/cofilin. siRNA knockdown, drug sensitivity assays, cell cycle analysis, Western blot for microtubule acetylation and TPPP1 PloS one Medium 23991158
2013 Limk2 mediates Sema3A (but not Sema3F) chemorepulsive signaling in cortical interneurons migrating through the subpallium; Limk2-siRNA-transfected interneurons fail to respond to Sema3A and aberrantly invade the developing striatum. siRNA knockdown, chemotactic assay, brain slice preparations, in utero electroporation Biology open Medium 23519094
2013 Limk2 deletion in mice increases colon tumor size in a colitis-associated colorectal cancer model and increases gastrointestinal stem cell proliferation, demonstrating a conserved role for LIMK2 in constraining stem cell proliferation. Limk2 knockout mouse model, colitis-associated CRC model, immunostaining for LIMK2 expression and substrate phosphorylation Gut Medium 23585469
2017 BMPR2 activates LIMK2 through the RhoA/ROCK pathway and also interacts directly with LIMK2; activated LIMK2 promotes phosphorylation of downstream signaling components driving osteosarcoma invasion and metastasis. iTRAQ-based phosphoproteomics, Western blot, co-immunoprecipitation, in vitro and in vivo invasion/metastasis assays Oncotarget Medium 28938584
2018 The LIMK2-1 isoform contains a C-terminal PP1 inhibitory domain absent in LIMK2a and LIMK2b. LIMK2-1 does not phosphorylate cofilin directly despite having kinase activity; instead it interacts with PP1 and partially inhibits PP1 activity toward cofilin, thereby indirectly maintaining phospho-cofilin levels and promoting actin stress fiber formation. Biochemical characterization, in vitro kinase assay, co-immunoprecipitation with PP1, PP1 activity assay, actin stress fiber imaging The Biochemical journal High 30373762
2019 LIMK2 directly phosphorylates TWIST1, stabilizing it by preventing its degradation; TWIST1 in turn stabilizes LIMK2 by inhibiting its ubiquitylation. Phosphorylation-dead TWIST1 acts as dominant negative and fully prevents EMT and tumor formation in vivo, establishing the LIMK2-TWIST1 signaling axis in CRPC. Chemical genetic substrate identification, in vitro kinase assay, site-directed mutagenesis, xenograft mouse model, ubiquitylation assay Cancer letters High 30716360
2020 LIMK2 phosphorylates PTEN at five sites, degrading it and inhibiting its activity, thereby activating PI3K/AKT oncogenic signaling. PTEN also degrades LIMK2 in a feedback loop (confirmed in PTEN-/- vs PTEN+/+ mouse prostates), identifying LIMK2 as the missing link between hypoxia and PTEN degradation in CRPC. In vitro kinase assay, site-directed mutagenesis, ubiquitylation assay, PTEN knockout mouse validation, xenograft model Cancer letters High 32931887
2020 LIMK2 degrades SPOP by direct phosphorylation at three sites; SPOP promotes LIMK2 ubiquitylation in a feedback loop. LIMK2-mediated SPOP degradation stabilizes AR, ARv7, and c-Myc. Phospho-resistant SPOP completely suppresses tumorigenesis in vivo. In vitro kinase assay, site-directed mutagenesis (phospho-resistant SPOP), ubiquitylation assay, xenograft mouse model British journal of cancer High 33311589
2020 LIMK2 inhibition blocks SRPK1 phosphorylation and its kinase activity; SRPK1 identified as a LIMK2 substrate by SILAC-based phosphoproteomics. Genetic or pharmacological inhibition of LIMK2 or SRPK1 equivalently blocks metastatic attributes of TNBC cells. SILAC-based phosphoproteomics, shRNA knockdown, pharmacological inhibition, in vivo metastasis mouse model Oncogenesis Medium 32859889
2021 LIMK2 directly phosphorylates NKX3.1, promoting its degradation in CRPC cells. NKX3.1 in turn promotes LIMK2 ubiquitylation. LIMK2 also downregulates NKX3.1 mRNA. LIMK2-NKX3.1 crosstalk regulates AR, ARv7, and AKT signaling. In vitro kinase assay, co-immunoprecipitation, ubiquitylation assay, Western blot, xenograft mouse model Cancers Medium 34066036
2021 LIMK2 phosphorylates cofilin to regulate F-actin dynamics in airway smooth muscle (ASM); LIMK2-deficient ASM shows ~30% inhibition of contractile force and reduced F/G-actin ratio. LIMK2 functions independently of cross-bridge movement and is required for 5-HT-evoked length-sensitive contraction but not acetylcholine-evoked contraction. LIMK2 knockout mouse, force measurements, F/G-actin ratio assay, phospho-cofilin Western blot Journal of genetics and genomics High 34353741
2023 LIMK2 phosphorylates G3BP1, and G3BP1 is required for ESM1 mRNA stability. LIMK2→G3BP1→ESM1 pathway promotes melanoma tumor growth and metastasis; G3BP1 knockdown mirrors LIMK2 inhibition and ESM1 ectopic expression rescues LIMK2 or G3BP1 inhibition. Phosphoproteomics, shRNA knockdown, RNA-seq, rescue experiments, in vivo mouse tumor models Oncogene Medium 36922679
2025 LIMK2 phosphorylates MST4 at T178, activating its kinase function; activated MST4 then phosphorylates NPM1 at T95, which is essential for centrosome clustering and tumor cell proliferation. LIMK2 knockout attenuates esophageal tumorigenesis in vivo; pharmacological LIMK2 inhibition disrupts centrosome clustering causing multipolar spindle assembly and apoptosis. In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, shRNA knockdown, xenograft and 4NQO mouse tumor models Oncogene High 40775397
2025 The LIMK2-1 isoform is phosphorylated predominantly by protein kinase C and, when phosphorylated, inhibits PP1 catalytic subunit (PP1c) isoforms and the myosin phosphatase (MP) holoenzyme with IC50 ~28–47 nM, functioning as a CPI-17-like phosphatase inhibitor. LIMK2-1 interacts with PP1c isoforms. Flag-LIMK2-1 overexpression, co-immunoprecipitation with PP1c, in vitro phosphatase activity assay, calyculin A treatment, phosphospecific antibody International journal of molecular sciences High 40806479
2019 LIMK2a knockout mice show prolonged bleeding after injury; LIMK2 protein is expressed in human and mouse platelets and LIMK2a-deficient mice exhibit impaired platelet spreading, aggregation, and thrombus formation, demonstrating a role for LIMK2 in platelet cytoskeletal function. LIMK2a knockout mouse, platelet spreading assay, aggregation assay, thrombus formation, Western blot Experimental cell research Medium 31926945
2021 LIMK2 depletion in human embryonic stem cells inhibits definitive endoderm generation and promotes neuroectodermal fate; knockdown reduces actin stress fiber assembly and cofilin phosphorylation, and impairs EMT-gene upregulation and cell migration during endodermal differentiation. siRNA knockdown, immunofluorescence for F-actin, Western blot for p-cofilin, RT-PCR for lineage markers In vitro cellular & developmental biology. Animal Medium 33977398
2022 TP receptor activation signals through Gα13-RhoA/C-ROCK-LIMK2 to inhibit angiogenic sprouting of human endothelial cells; pharmacological ROCK or LIMK2 inhibition reverses TP-agonist-induced endothelial cell tension and focal adhesion dysregulation. RNAi gene silencing, pharmacological inhibition, HUVEC spheroid sprouting assay, FRET biosensors for RhoA/C activity, live-cell imaging Biochemical pharmacology Medium 35525325

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 LIMK-1 and LIMK-2, two members of a LIM motif-containing protein kinase family. Oncogene 86 7651734
2009 LIMK1 and LIMK2 are important for metastatic behavior and tumor cell-induced angiogenesis of pancreatic cancer cells. Zebrafish 82 20047470
2019 Osteosarcoma cell intrinsic PD-L2 signals promote invasion and metastasis via the RhoA-ROCK-LIMK2 and autophagy pathways. Cell death & disease 68 30886151
2010 p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory RhoC to LIMK2 signaling pathway promotes cell survival. Cell research 68 21079653
2005 The neurofibromatosis type 1 gene product neurofibromin enhances cell motility by regulating actin filament dynamics via the Rho-ROCK-LIMK2-cofilin pathway. The Journal of biological chemistry 63 16169856
2019 NUDT21 inhibits bladder cancer progression through ANXA2 and LIMK2 by alternative polyadenylation. Theranostics 54 31695759
2012 LIMK2 is a crucial regulator and effector of Aurora-A-kinase-mediated malignancy. Journal of cell science 51 22492986
1997 Comparison of tissue distribution of two novel serine/threonine kinase genes containing the LIM motif (LIMK-1 and LIMK-2) in the developing rat. Brain research. Molecular brain research 49 9149099
2023 LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features. Cells 46 36899941
2006 Different activity regulation and subcellular localization of LIMK1 and LIMK2 during cell cycle transition. Experimental cell research 37 16455074
2020 LIMK2 promotes the metastatic progression of triple-negative breast cancer by activating SRPK1. Oncogenesis 35 32859889
2018 Imbalanced LIMK1 and LIMK2 expression leads to human colorectal cancer progression and metastasis via promoting β-catenin nuclear translocation. Cell death & disease 34 29970879
2012 Nf1 RasGAP inhibition of LIMK2 mediates a new cross-talk between Ras and Rho pathways. PloS one 34 23082153
2019 Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer. Cancer letters 32 30716360
2012 TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation. Journal of cell science 31 22328514
2020 VEGFR2 Promotes Metastasis and PD-L2 Expression of Human Osteosarcoma Cells by Activating the STAT3 and RhoA-ROCK-LIMK2 Pathways. Frontiers in oncology 30 33014879
2014 Novel LIMK2 Inhibitor Blocks Panc-1 Tumor Growth in a mouse xenograft model. Oncoscience 29 25593987
2013 Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation. Gut 29 23585469
1996 Subcellular localization and protein interaction of the human LIMK2 gene expressing alternative transcripts with tissue-specific regulation. Biochemical and biophysical research communications 28 8954941
2018 LIMK2 acts as an oncogene in bladder cancer and its functional SNP in the microRNA-135a binding site affects bladder cancer risk. International journal of cancer 27 30006972
2006 Upregulation of profilin, cofilin-2 and LIMK2 in cultured pulmonary artery smooth muscle cells and in pulmonary arteries of monocrotaline-treated rats. Vascular pharmacology 26 16524786
2019 MED12 exerts an emerging role in actin-mediated cytokinesis via LIMK2/cofilin pathway in NSCLC. Molecular cancer 25 31072327
2017 BMPR2 promotes invasion and metastasis via the RhoA-ROCK-LIMK2 pathway in human osteosarcoma cells. Oncotarget 25 28938584
2005 Inhibition of nuclear import of LIMK2 in endothelial cells by protein kinase C-dependent phosphorylation at Ser-283. The Journal of biological chemistry 25 15923181
2004 PDGF and IL-1beta upregulate cofilin and LIMK2 in canine cultured pulmonary artery smooth muscle cells. Journal of vascular research 23 15467300
2019 LIMK1 and LIMK2 regulate cortical development through affecting neural progenitor cell proliferation and migration. Molecular brain 22 31319858
1997 cDNA cloning, genomic organization, and chromosomal localization of the mouse LIM motif-containing kinase gene, Limk2. Biochemical and biophysical research communications 22 9425257
2021 LIMK2-NKX3.1 Engagement Promotes Castration-Resistant Prostate Cancer. Cancers 20 34066036
2020 Negative cross talk between LIMK2 and PTEN promotes castration resistant prostate cancer pathogenesis in cells and in vivo. Cancer letters 20 32931887
2020 Phosphorylation-dependent regulation of SPOP by LIMK2 promotes castration-resistant prostate cancer. British journal of cancer 20 33311589
2015 Endothelin-1 induces LIMK2-mediated programmed necrotic neuronal death independent of NOS activity. Molecular brain 20 26438559
2013 LIMK2 mediates resistance to chemotherapeutic drugs in neuroblastoma cells through regulation of drug-induced cell cycle arrest. PloS one 20 23991158
2012 Keratinocyte migration in the developing eyelid requires LIMK2. PloS one 20 23071748
1999 Cloning and characterization of the alternative promoter regions of the human LIMK2 gene responsible for alternative transcripts with tissue-specific expression. Gene 20 10452946
2019 Deletion of Limk1 and Limk2 in mice does not alter cochlear development or auditory function. Scientific reports 19 30833597
2008 ROCK1 and LIMK2 interact in spread but not blebbing cancer cells. PloS one 18 18852895
2014 Inhibition of FSS-induced actin cytoskeleton reorganization by silencing LIMK2 gene increases the mechanosensitivity of primary osteoblasts. Bone 17 25549868
2008 Effect of LIMK2 RNAi on reorganization of the actin cytoskeleton in osteoblasts induced by fluid shear stress. Journal of biomechanics 17 18805530
1997 Cloning and biochemical characterization of LIMK-2, a protein kinase containing two LIM domains. Journal of biochemistry 16 9089416
2013 Theoretical study on the interaction of pyrrolopyrimidine derivatives as LIMK2 inhibitors: insight into structure-based inhibitor design. Molecular bioSystems 15 23881296
2013 Limk2 mediates semaphorin signalling in cortical interneurons migrating through the subpallium. Biology open 13 23519094
2018 LIMK2-1, a new isoform of human LIMK2, regulates actin cytoskeleton remodeling via a different signaling pathway than that of its two homologs, LIMK2a and LIMK2b. The Biochemical journal 12 30373762
2023 LIMK2 promotes melanoma tumor growth and metastasis through G3BP1-ESM1 pathway-mediated apoptosis inhibition. Oncogene 11 36922679
2023 Stratifin (SFN) Regulates Cervical Cancer Cell Proliferation, Apoptosis, and Cytoskeletal Remodeling and Metastasis Progression Through LIMK2/Cofilin Signaling. Molecular biotechnology 11 37946061
2020 Metabolites of intestinal microflora upregulate miR-192-5p to suppress proliferation of colon cancer cells via RhoA-ROCK-LIMK2 pathway. European review for medical and pharmacological sciences 11 32141548
2023 LIMK2: A Multifaceted kinase with pleiotropic roles in human physiology and pathologies. Cancer letters 9 37141984
2019 Chronic administration of LIMK2 inhibitors alleviates cavernosal veno-occlusive dysfunction through suppression of cavernosal fibrosis in a rat model of erectile dysfunction after cavernosal nerve injury. PloS one 9 30870492
2022 Thromboxane A2 receptor activation via Gα13-RhoA/C-ROCK-LIMK2-dependent signal transduction inhibits angiogenic sprouting of human endothelial cells. Biochemical pharmacology 8 35525325
2020 LIM kinase 2 (LIMK2) may play an essential role in platelet function. Experimental cell research 8 31926945
2018 LIMK2-1 is a Hominidae-Specific Isoform of LIMK2 Expressed in Central Nervous System and Associated with Intellectual Disability. Neuroscience 6 30594563
2024 Decoding the tumour-modulatory roles of LIMK2. Life sciences 5 38580197
2021 Involvement of LIMK2 in actin cytoskeleton remodeling during the definitive endoderm differentiation. In vitro cellular & developmental biology. Animal 5 33977398
2021 LIMK2 is required for membrane cytoskeleton reorganization of contracting airway smooth muscle. Journal of genetics and genomics = Yi chuan xue bao 5 34353741
2020 mRNA level of ROCK1, RHOA, and LIMK2 as genes associated with apoptosis in evaluation of effectiveness of adalimumab treatment. Pharmacological reports : PR 5 32124389
2024 Unveiling novel type 1 inhibitors for targeting LIM kinase 2 (LIMK2) for cancer therapeutics: An integrative pharmacoinformatics approach. Computational biology and chemistry 3 39631222
2023 NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2. Open life sciences 3 37077345
2022 Function of connexin 43 and RhoA/LIMK2/Cofilin signaling pathway in transient changes of contraction and dilation of human umbilical arterial smooth muscle cells. The international journal of biochemistry & cell biology 2 36330887
2023 Harnessing allosteric inhibition: prioritizing LIMK2 inhibitors for targeted cancer therapy through pharmacophore-based virtual screening and essential molecular dynamics. Journal of biomolecular structure & dynamics 1 38063080
2009 [Effects of LIMK2 RNA interference on the mechanosensitivity of c-fos gene in osteoblast]. Zhonghua yi xue za zhi 1 20193279
1998 A sequence highly similar to PNG is located on chromosome 22q12 in intron 15 of the LIMK-2 gene. Biochemistry and molecular biology international 1 9556220
2026 LIMK2 inactivation suppresses mechanical stimulation-induced dermal fibroblast differentiation and resistance to apoptosis. Scientific reports 0 41644972
2026 Ift46 deficiency causes renal cyst via enhanced Limk2 through lack of autophagy flux. Cell communication and signaling : CCS 0 41680856
2026 Discovery and Development of a Potent LIMK2 Isoform-Specific Degrader. ACS chemical biology 0 42066056
2026 Rare variants in TTC7A, ROCK2 and LIMK2 suggest a role for the ROCK-signaling pathway in isolated intestinal malrotation. Pediatric surgery international 0 42185554
2025 LIMK2 promotes centrosome clustering and cancer progression by activating MST4-mediated phosphorylation of NPM1. Oncogene 0 40775397
2025 LIMK2-1 Is a Phosphorylation-Dependent Inhibitor of Protein Phosphatase-1 Catalytic Subunit and Myosin Phosphatase Holoenzyme. International journal of molecular sciences 0 40806479

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