Affinage

LIMK2

LIM domain kinase 2 · UniProt P53671

Length
638 aa
Mass
72.2 kDa
Annotated
2026-04-28
64 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIMK2 is a LIM-domain-containing serine/threonine kinase that functions as a central integrator of Rho-ROCK, Aurora A, and PKC-δ signaling to regulate actin cytoskeleton dynamics, mitotic spindle organization, cell migration, and diverse transcriptional and signaling outputs. Its best-characterized activity is phosphorylation and inactivation of cofilin, which stabilizes F-actin and is required for keratinocyte migration, platelet function, airway smooth muscle contraction, cortical neuronal migration, and gastrointestinal stem cell homeostasis (PMID:23071748, PMID:31926945, PMID:34353741, PMID:31319858, PMID:23585469). Beyond cofilin, LIMK2 directly phosphorylates substrates including TWIST1, PTEN, SPOP, NKX3.1, SRPK1, G3BP1, and MST4—often engaging in reciprocal feedback loops that control substrate stability—thereby driving epithelial-mesenchymal transition, androgen receptor signaling in castration-resistant prostate cancer, metastasis, and centrosome clustering (PMID:30716360, PMID:32931887, PMID:33311589, PMID:32859889, PMID:36922679, PMID:40775397). The LIMK2-1 splice isoform lacks direct cofilin kinase activity and instead functions as a potent CPI-17-like inhibitor of PP1/myosin phosphatase upon PKC-mediated phosphorylation, providing an alternative mechanism for cytoskeletal regulation (PMID:30373762, PMID:40806479).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Establishing LIMK2 as a bona fide serine/threonine kinase answered the fundamental question of whether this LIM-domain protein possessed intrinsic catalytic activity.

    Evidence In vitro kinase assay with immunoprecipitated LIMK2 phosphorylating MBP

    PMID:7651734

    Open questions at the time
    • Physiological substrates unidentified
    • Upstream activators unknown
    • Relationship to actin cytoskeleton not established
  2. 1996 Medium

    Isoform-specific localization studies revealed that the LIM/PDZ domains control cytoplasmic vs. nuclear distribution, establishing that LIMK2 functions in multiple subcellular compartments.

    Evidence Transfection and localization of LIMK2a, LIMK2b, and kinase-only constructs with Co-IP

    PMID:8954941

    Open questions at the time
    • Nuclear function undefined
    • Nuclear import mechanism unknown
    • Associated proteins at 63/58 kDa unidentified
  3. 2005 High

    Placing LIMK2 downstream of Rho-ROCK in a cofilin-phosphorylating cascade resolved its principal physiological pathway and linked it to actin stress fiber formation and cell motility.

    Evidence siRNA knockdown of NF1 with epistasis analysis separating Ras-Raf/PI3K/RalGEF from Rho-ROCK-LIMK2

    PMID:16169856

    Open questions at the time
    • Direct ROCK-LIMK2 phosphorylation sites not mapped
    • Non-cofilin substrates unknown
    • In vivo relevance not demonstrated
  4. 2005 High

    Discovery that PKC-δ phosphorylates LIMK2 at Ser-283 to block nuclear import established a regulated mechanism for controlling LIMK2 subcellular distribution and cell cycle progression.

    Evidence In vitro phosphorylation by PKC-δ; Ser-283 mutagenesis; FRAP and live imaging of EGFP-LIMK2

    PMID:15923181

    Open questions at the time
    • Nuclear substrates of LIMK2 not identified beyond cyclin D1 regulation
    • Whether Ser-283 phosphorylation affects kinase activity per se untested
  5. 2006 High

    Demonstration that LIMK2 localizes to the mitotic spindle and spindle midzone with increased cofilin kinase activity during mitosis extended its role beyond interphase actin regulation to cell division.

    Evidence Immunofluorescence with cell-cycle synchronization; in vitro kinase assay on mitotic extracts

    PMID:16455074

    Open questions at the time
    • Mitotic LIMK2 activating kinase not identified at this point
    • Whether spindle localization requires cofilin phosphorylation unclear
  6. 2008 High

    FRET-based demonstration that ROCK1 preferentially interacts with LIMK2 in polarized/spread cells showed the ROCK1–LIMK2 axis is specific to mesenchymal-mode migration, not blebbing.

    Evidence FRET and Co-IP in cancer cells with distinct morphological modes

    PMID:18852895

    Open questions at the time
    • ROCK2 vs. ROCK1 selectivity for LIMK2 not fully resolved
    • Structural basis of mesenchymal-specific interaction unknown
  7. 2010 High

    Identification of LIMK2 as a direct p53 target gene linked cytoskeletal remodeling to the DNA damage response, revealing a pro-survival role for LIMK2 after genotoxic stress.

    Evidence ChIP confirming p53 occupancy at LIMK2 promoter; siRNA and pharmacological inhibition sensitizing cells to radio/chemotherapy

    PMID:21079653

    Open questions at the time
    • Precise p53-binding element not fine-mapped
    • Whether cofilin is the relevant substrate in this survival context unknown
  8. 2012 High

    Multiple studies converged to define LIMK2's in vivo roles: Aurora A directly phosphorylates and activates LIMK2 creating a positive feedback loop essential for tumorigenesis; LIMK2 regulates astral microtubules through TPPP; NF1 SecPH domain specifically inhibits LIMK2 (not LIMK1); and LIMK2 knockout causes eyes-open-at-birth due to failed keratinocyte migration.

    Evidence Chemical genetics (Aurora A analog-sensitive kinase); RNAi epistasis for TPPP; Y2H/Co-IP for NF1-LIMK2; LIMK2 knockout mouse phenotyping

    PMID:22328514 PMID:22492986 PMID:23071748 PMID:23082153

    Open questions at the time
    • Whether Aurora A and ROCK phosphorylation of LIMK2 are cooperative or competitive
    • TPPP phosphorylation by LIMK2 not directly demonstrated
    • Structural basis of NF1 SecPH selectivity for LIMK2 over LIMK1 unknown
  9. 2013 High

    Loss-of-function studies in mice and Drosophila revealed a conserved role for LIMK2 in restraining gastrointestinal stem cell proliferation, and LIMK2 was shown to mediate Sema3A signaling in cortical interneurons for proper neuronal migration.

    Evidence LIMK2 knockout mice and Drosophila LIMK knockdown for GI homeostasis; siRNA and in utero electroporation for neuronal migration

    PMID:23519094 PMID:23585469

    Open questions at the time
    • Downstream substrate in GI stem cells not identified
    • Whether cofilin or another substrate mediates Sema3A response unresolved
  10. 2018 High

    Characterization of the LIMK2-1 splice isoform revealed it lacks cofilin kinase activity and instead functions as a PP1 inhibitor, providing an entirely distinct mechanism for cytoskeletal regulation.

    Evidence In vitro kinase assay showing no cofilin phosphorylation; Co-IP with PP1; actin stress fiber assay

    PMID:30373762

    Open questions at the time
    • Tissue distribution and expression ratio of LIMK2-1 vs. other isoforms incompletely defined
    • PP1 inhibitory domain not structurally characterized
  11. 2019 High

    Identification of TWIST1 as a direct LIMK2 substrate that reciprocally stabilizes LIMK2 revealed a kinase-transcription factor feedback axis driving EMT in castration-resistant prostate cancer.

    Evidence In vitro phosphorylation; phosphorylation-dead dominant-negative TWIST1; xenograft tumor assays

    PMID:30716360

    Open questions at the time
    • Specific TWIST1 phosphorylation sites by LIMK2 not fully mapped
    • Whether this axis operates outside prostate cancer untested
  12. 2020 High

    A burst of substrate discovery established LIMK2 as a multi-substrate kinase: it phosphorylates and degrades PTEN and SPOP (each in feedback loops), activates SRPK1 to promote metastasis, and is required for platelet function in vivo.

    Evidence Direct in vitro phosphorylation with site mapping for PTEN and SPOP; SILAC phosphoproteomics for SRPK1; LIMK2a knockout mouse for platelet assays

    PMID:31926945 PMID:32859889 PMID:32931887 PMID:33311589

    Open questions at the time
    • How LIMK2 substrate selectivity is determined (cofilin vs. non-cofilin targets) unknown
    • Whether PTEN/SPOP regulation occurs in non-prostate tissues untested
    • Platelet phenotype rescue experiments not performed
  13. 2021 High

    NKX3.1 was added as another LIMK2 substrate in a mutual degradation loop regulating AR signaling, while LIMK2 knockout studies demonstrated its requirement for airway smooth muscle contraction through cofilin-dependent actin remodeling.

    Evidence Direct phosphorylation and ubiquitylation assays for NKX3.1; LIMK2 KO mouse force transduction and F/G-actin ratio measurements

    PMID:34066036 PMID:34353741

    Open questions at the time
    • Whether LIMK2 regulation of AR signaling depends on NKX3.1 phosphorylation alone or also on SPOP/PTEN degradation
    • Mechanism connecting cofilin to smooth muscle actin polymerization vs. myosin regulation not delineated
  14. 2023 High

    Phosphoproteomic identification of G3BP1 as a LIMK2 substrate linked LIMK2 to mRNA stability regulation through a LIMK2→G3BP1→ESM1 axis in melanoma.

    Evidence Phosphoproteomics; shRNA; RNA-seq; mRNA stability assay; in vivo melanoma model

    PMID:36922679

    Open questions at the time
    • Whether G3BP1 phosphorylation by LIMK2 affects stress granule dynamics untested
    • Broader RNA targets beyond ESM1 not defined
  15. 2025 High

    Discovery that LIMK2 phosphorylates MST4 at T178 to activate a MST4→NPM1 cascade for centrosome clustering revealed a new mechanism for LIMK2-driven tumor proliferation, while quantitative IC50 measurements established LIMK2-1 as a nanomolar-potency myosin phosphatase inhibitor.

    Evidence In vitro kinase assay with site-specific mutagenesis and in vivo esophageal tumorigenesis model for MST4; reconstituted phosphatase inhibition assay with IC50 for LIMK2-1

    PMID:40775397 PMID:40806479

    Open questions at the time
    • Whether LIMK2-MST4-NPM1 operates in non-esophageal cancers untested
    • Relative contribution of LIMK2-1 PP1 inhibition vs. canonical LIMK2 cofilin phosphorylation in vivo unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LIMK2 achieves substrate selectivity among its numerous substrates (cofilin, TWIST1, PTEN, SPOP, NKX3.1, SRPK1, G3BP1, MST4), whether there is a unifying structural or scaffold-based mechanism, and how isoform-specific functions (LIMK2a kinase vs. LIMK2-1 phosphatase inhibitor) are coordinated in vivo remain major open questions.
  • No structural model of LIMK2 in complex with any substrate
  • Isoform expression ratio across tissues not systematically mapped
  • No comprehensive phosphosite atlas of LIMK2 autophosphorylation or upstream regulation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 12 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1643685 Disease 6 R-HSA-1640170 Cell Cycle 4 R-HSA-1266738 Developmental Biology 3 R-HSA-5357801 Programmed Cell Death 1
Partners
AURKACFL1NF1PPP1CAPTENROCK1SPOPTWIST1

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 with two N-terminal LIM motifs and a C-terminal kinase domain; it phosphorylates serine and threonine residues of exogenous substrates (e.g., myelin basic protein) in vitro, confirming its kinase activity. In vitro kinase assay with immunoprecipitated protein Oncogene High 7651734
1997 Recombinant LIMK2 is autophosphorylated and exhibits serine/threonine kinase activity toward exogenous substrate MBP; endogenous LIMK2 co-precipitates with a 140 kDa tyrosine-phosphorylated protein; LIMK2 localizes to both nucleus and Triton X-100 soluble cytoplasmic fraction. In vitro kinase assay; co-immunoprecipitation; subcellular fractionation Journal of biochemistry High 9089416
1996 LIMK2a (with two LIM domains, PDZ domain, and kinase domain) is distributed in cytoplasm and nucleus, whereas LIMK2b (with one and a half LIM domains) is mainly cytoplasmic; a truncated LIMK2-Kinase construct localizes to the nucleus without showing protein association. Transfection and subcellular localization studies; Co-IP identifying associated 63 kDa and 58 kDa proteins Biochemical and biophysical research communications Medium 8954941
2005 LIMK2 is a downstream effector of the Rho-ROCK pathway; loss of neurofibromin activates Rho-ROCK-LIMK2 signaling, increasing cofilin phosphorylation and actin stress fiber formation, thereby enhancing cell motility. This pathway requires Ras activation but is independent of Raf, PI3K, and RalGEF. siRNA knockdown of NF1; immunofluorescence; western blotting; genetic epistasis The Journal of biological chemistry High 16169856
2005 PKC-delta phosphorylates LIMK2 at Ser-283 (between PDZ and kinase domains), inhibiting nuclear import of LIMK2 in endothelial cells; this is a mechanism to relieve LIMK2-mediated suppression of cyclin D1 expression and promote G1-to-S transition. EGFP-LIMK2 live imaging; FRAP; leptomycin B treatment; in vitro phosphorylation by PKC-delta; site-directed mutagenesis (Ser-283) The Journal of biological chemistry High 15923181
2006 LIMK2 activity toward cofilin is markedly increased when cells are arrested in mitosis by microtubule disruption (nocodazole); LIMK2 localizes to the mitotic spindle during prometaphase and to the spindle midzone during anaphase/telophase, distinct from LIMK1's localization at spindle poles and the cleavage furrow. Immunofluorescence; cell synchronization with nocodazole; in vitro kinase assay Experimental cell research High 16455074
2010 LIMK2 is a direct p53 target gene induced by genotoxic agents; activation of LIMK2 downstream of the RhoC-p53 axis has a pro-survival function following DNA damage, and LIMK inhibition sensitizes cells to radio- or chemotherapy. siRNA knockdown; pharmacological inhibition; ChIP (p53 target gene identification); cell viability assays Cell research High 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 (positive feedback loop); LIMK2 ablation fully abrogates Aurora-A-mediated tumorigenesis in vivo. Chemical genetic approach (analog-sensitive kinase); direct phosphorylation assays; site-directed mutagenesis; nude mouse xenograft Journal of cell science High 22492986
2012 LIMK2 acts downstream of RhoA-ROCK in regulating astral microtubule organization through TPPP (not cofilin), while both LIMK1 and LIMK2 affect centrosome focusing; these activities regulate spindle orientation in mitotic cells. RNAi knockdown; immunofluorescence; epistasis analysis Journal of cell science High 22328514
2012 The NF1 RasGAP SecPH domain directly interacts with LIMK2 (but not LIMK1), partially inhibits LIMK2 kinase activity on cofilin, and specifically prevents LIMK2 activation by ROCK, establishing a cross-talk between Ras and Rho/ROCK/LIMK2/cofilin pathways. Yeast two-hybrid screen; co-immunoprecipitation; in vitro kinase assay PloS one High 23082153
2012 LIMK2 is required for keratinocyte migration during eyelid development in vivo; LIMK2 knockout mice show eyes-open-at-birth phenotype due to failure of leading keratinocytes to nucleate filamentous actin, associated with reduced phospho-cofilin levels. LIMK2 knockout mouse; histology; immunostaining for F-actin and phospho-cofilin PloS one High 23071748
2013 LIMK2 deletion increases gastrointestinal stem cell proliferation in mice and Drosophila, revealing a conserved role for LIMK2 in constraining gastrointestinal stem cell homeostasis. Limk2 knockout mice; Drosophila LIMK knockdown; histology; mouse cancer model Gut High 23585469
2013 Limk2 mediates Sema3A (but not Sema3F) signaling in cortical interneurons; Limk2 siRNA-transfected interneurons are less responsive to Sema3A, leading to aberrant invasion of the developing striatum. siRNA knockdown; chemotactic assays; brain slice preparation; in utero electroporation Biology open Medium 23519094
2008 ROCK1 directly interacts with LIMK2 (preferred substrate for ROCK1) in polarized/spread cancer cells but not in blebbing cells, as demonstrated by FRET; LIMK2 does not induce membrane blebbing, indicating the ROCK1:LIMK2 pathway is specific to mesenchymal-mode migration. FRET; Co-IP; functional migration assays PloS one High 18852895
2019 LIMK2 directly phosphorylates TWIST1, stabilizing it; TWIST1 also stabilizes LIMK2 by inhibiting its ubiquitylation; phosphorylation-dead TWIST1 acts as dominant negative and prevents EMT and tumor formation in vivo, establishing LIMK2-TWIST1 as a signaling axis in CRPC. In vitro phosphorylation; dominant-negative mutant; in vivo xenograft; ubiquitylation assay Cancer letters High 30716360
2020 LIMK2 phosphorylates PTEN at five sites, promoting its degradation and inhibiting its activity; PTEN in turn degrades LIMK2 in a feedback loop; LIMK2 is the missing link between hypoxia and PTEN degradation in CRPC. In vitro phosphorylation; site mapping; PTEN-/- and PTEN+/+ mouse prostates; xenograft Cancer letters High 32931887
2020 LIMK2 directly phosphorylates and degrades SPOP (E3 ubiquitin ligase adaptor) at three sites; SPOP in turn promotes LIMK2 ubiquitylation (feedback loop); SPOP degradation stabilizes AR, ARv7, and c-Myc; phospho-resistant SPOP completely suppresses tumorigenesis in vivo. Innovative direct target identification technique; in vitro phosphorylation; ubiquitylation assay; xenograft British journal of cancer High 33311589
2021 NKX3.1 is directly phosphorylated and degraded by LIMK2; NKX3.1 in turn promotes LIMK2 ubiquitylation; this LIMK2-NKX3.1 feedback loop regulates AR, ARv7, and AKT signaling in CRPC. Direct phosphorylation assay; ubiquitylation assay; in vivo xenograft; biochemical assays Cancers High 34066036
2020 LIMK2 promotes TNBC metastasis through phosphorylation and activation of SRPK1 (serine/arginine protein kinase); LIMK2 inhibition blocks SRPK1 phosphorylation and activity, and pharmacological inhibition of LIMK2 blocks metastasis in mice without affecting primary tumor growth. SILAC-based phosphoproteomics; shRNA knockdown; pharmacological inhibition; in vivo metastasis model Oncogenesis High 32859889
2018 The LIMK2-1 isoform contains a PP1 inhibitory domain at its C-terminus; it does not directly phosphorylate cofilin but interacts with PP1 and partially inhibits its activity toward cofilin, regulating actin cytoskeleton dynamics by preventing PP1-mediated cofilin dephosphorylation. Biochemical characterization; in vitro kinase assay; Co-IP with PP1; actin stress fiber assay The Biochemical journal High 30373762
2019 LIMK1 and LIMK2 regulate cortical development by controlling neural progenitor cell proliferation and neuronal migration; LIMK2 KO mice show reduced pyramidal neurons in upper cortical layers with a smaller progenitor pool and impaired neuronal migration. LIMK2 knockout mice; histology; cell counting Molecular brain Medium 31319858
2021 LIMK2 is required for membrane cytoskeleton reorganization in airway smooth muscle; LIMK2 deletion causes ~30% inhibition of contractile force, reduced cofilin phosphorylation, decreased F/G-actin ratio, and abolishes stretching-induced suppression of 5-HT-evoked force; LIMK2 acts independently of cross-bridge movement. LIMK2 knockout mice; force transduction assays; F/G-actin ratio measurement; western blotting Journal of genetics and genomics High 34353741
2015 Endothelin-1 acts upstream of LIMK2 via ETB receptor and ROCK1 to induce programmed necrotic neuronal death; ET-1/ETB/ROCK1/LIMK2 signaling impairs DRP1-mediated mitochondrial fission, leading to neuronal necrosis. ETB receptor antagonist (BQ788); western blotting; in vivo status epilepticus model Molecular brain Medium 26438559
2017 BMPR2 directly interacts with LIMK2 and activates it through the RhoA/ROCK pathway; LIMK2 phosphorylation by BMPR2 is crucial for BMPR2-mediated pro-metastatic signaling in osteosarcoma cells. iTRAQ-based phosphoproteomic analysis; western blotting; Co-IP (direct interaction); in vivo orthotopic model Oncotarget Medium 28938584
2025 LIMK2 phosphorylates MST4 at threonine 178 (T178), activating its kinase function; activated MST4 then phosphorylates NPM1 at T95, which is essential for centrosome clustering and tumor cell proliferation; LIMK2 knockout significantly attenuates esophageal tumorigenesis in vivo. In vitro kinase assay; site-specific mutagenesis; genetic depletion; in vivo 4NQO tumorigenesis model; pharmacological inhibition Oncogene High 40775397
2025 LIMK2-1 isoform is phosphorylated predominantly by protein kinase C; phosphorylated LIMK2-1 inhibits PP1 catalytic subunit isoforms and the myosin phosphatase holoenzyme with IC50 ~28–47 nM, functioning as a CPI-17-like phosphatase inhibitor. Co-IP with PP1c isoforms; in vitro phosphatase inhibition assay; overexpression in tsA201 cells International journal of molecular sciences High 40806479
2020 LIMK2a knockout mice show prolonged bleeding and defects in platelet spreading, aggregation, and thrombus formation, demonstrating an essential role for LIMK2 in platelet actin cytoskeleton-dependent functions. LIMK2a knockout mouse; bleeding time assay; platelet spreading assay; aggregation assay Experimental cell research Medium 31926945
2023 LIMK2 phosphorylates G3BP1 as a key direct substrate; G3BP1 inhibition mirrors LIMK2 inhibition; G3BP1 regulates ESM1 mRNA stability downstream, defining a LIMK2→G3BP1→ESM1 pathway promoting melanoma growth and metastasis. Phosphoproteomics; shRNA knockdown; RNA-seq; mRNA stability assay; in vivo tumor model Oncogene High 36922679
2022 Thromboxane A2 receptor activation signals through Gα13-RhoA/C-ROCK-LIMK2 to inhibit angiogenic sprouting of endothelial cells and induce endothelial cell contraction, tension, and focal adhesion dysregulation. RNAi-mediated silencing; pharmacological inhibition; FRET biosensors for RhoA/C; HUVEC spheroid sprouting assay Biochemical pharmacology Medium 35525325

Source papers

Stage 0 corpus · 64 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 81 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 51 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 41 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 34 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
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
2021 LIMK2-NKX3.1 Engagement Promotes Castration-Resistant Prostate Cancer. Cancers 18 34066036
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 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 promotes melanoma tumor growth and metastasis through G3BP1-ESM1 pathway-mediated apoptosis inhibition. Oncogene 10 36922679
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
2023 LIMK2: A Multifaceted kinase with pleiotropic roles in human physiology and pathologies. Cancer letters 8 37141984
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
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
2018 LIMK2-1 is a Hominidae-Specific Isoform of LIMK2 Expressed in Central Nervous System and Associated with Intellectual Disability. Neuroscience 5 30594563
2024 Decoding the tumour-modulatory roles of LIMK2. Life sciences 4 38580197
2020 mRNA level of ROCK1, RHOA, and LIMK2 as genes associated with apoptosis in evaluation of effectiveness of adalimumab treatment. Pharmacological reports : PR 4 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
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
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
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 0 38063080