Affinage

LIMK1

LIM domain kinase 1 · UniProt P53667

Length
647 aa
Mass
72.6 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 32 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

LIMK1 is a serine/threonine protein kinase that links upstream Rho-family signaling to actin cytoskeletal remodeling by phosphorylating the actin-depolymerizing factor cofilin at Ser3, thereby stabilizing F-actin (PMID:12123613, PMID:12775580). Its catalytic activity depends on the conserved IHRDL active-site residue D460, and the enzyme autophosphorylates on serine, threonine, and tyrosine (PMID:7478547); crystal structures of the kinase domain define its 'rock-and-poke' catalytic mechanism, substrate specificity, and dependence on activation-loop phosphorylation (PMID:31652302). LIMK1 is engaged downstream of ROCK in mechanosensing and stress-fiber maintenance (PMID:12775580, PMID:15199148), and is activated by multiple upstream kinases through phosphorylation of its activation loop (Thr508), including PAK2, PAK4, PAK6, and PKA (PMID:15908432, PMID:18424072, PMID:19424295, PMID:25714010). Its output is locally controlled by direct binding partners: BMPR-II binds and inhibits LIMK1 until BMP ligand relieves the block and Cdc42 synergizes to activate it during dendritogenesis and axon extension (PMID:12963706, PMID:15538389, PMID:19361494); LATS1 inhibits LIMK1 at the contractile ring during cytokinesis (PMID:15220930); TrkB drives BDNF-dependent LIMK1 dimerization and transphosphorylation (PMID:23086941); and adaptors such as LRAP25-MRCK confine LIMK1 activation to the lamellipodium (PMID:25107909). LIMK1 localizes to the Golgi via its LIM domain and to growth cones via its PDZ domain, where it regulates vesicle traffic and axon formation (PMID:15090620), and it shows cell-cycle-dependent redistribution to spindle poles and the cleavage furrow (PMID:16455074). Beyond cofilin, LIMK1 phosphorylates Tyr573 of MT1-MMP to regulate invadopodia and matrix degradation (PMID:27116935). In vivo, LIMK1 controls dendritic spine morphology, hippocampal LTP, and—via interaction with CREB—late-phase LTP and long-term memory (PMID:12123613, PMID:25645926), and LIMK-dependent actin remodeling in sensory neurons drives inflammatory heat hyperalgesia through TRPV1 (PMID:24962708). ROCK2-LIMK1 signaling mediates Aβ42-induced dendritic spine degeneration, and LIMK1 inhibition rescues spine loss in an Alzheimer's disease mouse model (PMID:31239325).

Mechanistic history

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

    Established that LIMK1 is a catalytically active protein kinase and identified the active-site residue required for activity, defining its enzymatic identity.

    Evidence In vitro kinase/autophosphorylation assays with GST-Limk1 and D460A active-site mutagenesis; MBP substrate phosphorylation

    PMID:7478547 PMID:7651734

    Open questions at the time
    • Physiological substrate not yet identified
    • No structural basis for catalysis
    • Upstream activators unknown
  2. 2002 High

    Defined cofilin as the in vivo LIMK1 substrate and connected the kinase to spine morphogenesis and synaptic plasticity, moving LIMK1 from a biochemical activity to a physiological regulator of the actin cytoskeleton.

    Evidence LIMK1 knockout mice with p-cofilin immunoblotting, LTP electrophysiology, and learning/memory behavioral tests

    PMID:12123613

    Open questions at the time
    • Upstream activating signals in neurons not resolved
    • Direct CREB/transcriptional link not yet established
    • Mechanism of spine actin regulation not fully defined
  3. 2003 High

    Identified BMPR-II as a direct binding partner that inhibits LIMK1 until BMP ligand relieves the block, establishing a ligand-gated mode of LIMK1 regulation and a Smad-independent BMP pathway.

    Evidence Yeast two-hybrid, Co-IP, in vitro cofilin phosphorylation, and PPH-associated truncation mutant analysis

    PMID:12963706

    Open questions at the time
    • Structural basis of inhibition not defined
    • How ligand binding relieves inhibition mechanistically unclear
  4. 2003 Medium

    Placed LIMK1 within the Rho-ROCK-cofilin mechanosensing cascade, ordering it downstream of ROCK and upstream of cofilin.

    Evidence Dominant-negative epistasis (RhoA, ROCK, LIMK, cofilin) with SREBP reporter assays in endothelial cells

    PMID:12775580

    Open questions at the time
    • Direct ROCK phosphorylation of LIMK1 not shown here
    • Restricted to a single signaling output (SREBP)
  5. 2004 High

    Resolved LIMK1 subcellular targeting and demonstrated domain-specific localization with functional consequences for Golgi traffic and axon formation.

    Evidence Confocal microscopy, fractionation, wild-type vs kinase-dead constructs, and constitutively active cofilin rescue

    PMID:15090620 PMID:16455074

    Open questions at the time
    • LIM-domain Golgi anchor partner not identified
    • Functional role of spindle-pole/cleavage-furrow localization not tested
  6. 2004 High

    Identified LATS1 and BMPR-II/Cdc42 as context-specific regulators, showing LIMK1 is negatively controlled during cytokinesis and positively activated during dendritogenesis.

    Evidence GST pull-down, Co-IP, immunofluorescence, antibody microinjection, siRNA, and KO mice (LATS1); reciprocal Co-IP and dendrite assays (BMPR-II/Cdc42)

    PMID:15220930 PMID:15538389

    Open questions at the time
    • Mechanism by which LATS1 inhibits the kinase unresolved
    • How Cdc42 synergizes with BMPR-II binding not structurally defined
  7. 2005 High

    Mapped multiple PAK-family kinases as direct upstream activators that phosphorylate LIMK1's activation loop, establishing PAK→LIMK1→cofilin as a recurring motility axis.

    Evidence siRNA epistasis, Co-IP, FRET-FLIM, in vitro phosphorylation (including Thr508 mapping), and migration/invasion assays across PAK2, PAK4, PAK6

    PMID:15908432 PMID:18424072 PMID:25714010

    Open questions at the time
    • Selectivity among PAK isoforms in different tissues not resolved
    • Quantitative contribution of each PAK to activation-loop phosphorylation unclear
  8. 2009 High

    Demonstrated a Rho-independent route to LIMK1 activation via direct PKA phosphorylation, broadening the upstream input map beyond Rho-GTPase signaling.

    Evidence Prkar1a-/- MEFs, pharmacological PKA activation, in vitro phosphorylation of Limk1 by PKA, and Rho/Rac inhibitor epistasis

    PMID:19424295

    Open questions at the time
    • PKA target residue on LIMK1 not defined
    • Crosstalk with Rho-driven activation not characterized
  9. 2012 Medium

    Expanded LIMK1 regulation to receptor- and scaffold-driven mechanisms—TrkB-induced dimerization/transphosphorylation, fascin-1 complex formation, and LRAP25-MRCK localized activation.

    Evidence Reciprocal Co-IP, FRET-FLIM, dominant-negative constructs, and functional actin/migration readouts

    PMID:22883572 PMID:23086941 PMID:25107909

    Open questions at the time
    • Stoichiometry of LIMK1 dimers not defined
    • Direct vs indirect nature of some interactions not fully validated
  10. 2013 Medium

    Identified DAPK as a scaffold for the LIMK/cofilin complex in TNF-induced apoptosis, linking LIMK1 to programmed cell death signaling.

    Evidence Peptide array, siRNA, DAPK inhibitor and overexpression, phospho-immunoblotting (LIMK Thr508, cofilin Ser3), and immunofluorescence

    PMID:23702034

    Open questions at the time
    • Whether DAPK directly phosphorylates LIMK1 not established
    • Structural model is computational
  11. 2015 High

    Established a LIMK1→CREB axis required selectively for late-phase LTP and long-term memory, revealing a transcriptional output distinct from acute actin regulation.

    Evidence LIMK1 KO mice, Co-IP for LIMK1-CREB interaction, L-LTP electrophysiology, memory testing, and CREB-activator rescue

    PMID:25645926

    Open questions at the time
    • Mechanism by which LIMK1 regulates CREB activity unresolved
    • Whether kinase activity is required for the CREB effect not defined
  12. 2016 High

    Identified MT1-MMP Tyr573 as a non-cofilin LIMK1 substrate, demonstrating that LIMK1 directly regulates invadopodia and matrix degradation beyond actin filament dynamics.

    Evidence Co-IP, in vitro kinase assay mapping Y573, Y573 mutagenesis, cortactin association, and invadopodia/matrix degradation assays

    PMID:27116935

    Open questions at the time
    • Full repertoire of non-cofilin substrates unknown
    • Tyrosine kinase activity scope not broadly characterized
  13. 2019 High

    Demonstrated disease-relevant LIMK1 functions—ROCK2-LIMK1 mediating Aβ42-induced spine degeneration with inhibitor rescue—while delineating where LIMK1 is dispensable (apoptotic blebbing) and solving the kinase-domain structure.

    Evidence Hippocampal cultures, ROCK1/2 dissection, LIMK1 inhibitor in hAPP mice (spine loss); CRISPR LIMK1 KO negative result for blebbing; X-ray crystallography with inhibitors

    PMID:31043701 PMID:31239325 PMID:31652302

    Open questions at the time
    • In vivo selectivity of LIMK1 inhibitors not fully addressed
    • Structural basis for partner-mediated regulation not captured in isolated kinase-domain structures
  14. 2014 High

    Established LIMK1-dependent actin remodeling as a driver of inflammatory pain via TRPV1 regulation, linking the kinase to nociceptor sensitization.

    Evidence In vivo CFA rat model, LIMK knockdown, cofilin phosphorylation and actin polymerization assays, and TRPV1 electrophysiology/behavior

    PMID:24962708

    Open questions at the time
    • Mechanism connecting actin polymerization to TRPV1 phosphorylation not fully defined
    • Whether LIMK1 acts on TRPV1 directly not established
  15. 2020 Medium

    Identified post-transcriptional control of LIMK1 by m6A reader YTHDC2, linking LIMK1 abundance to ER stress and chemoresistance.

    Evidence YTHDC2 siRNA, m6A site mutation, mRNA stability assay, eIF2α phospho-immunoblotting, and 5-FU sensitivity assays

    PMID:37778684

    Open questions at the time
    • Generality of LIMK1 m6A regulation across tissues unknown
    • Mechanism by which LIMK1 promotes eIF2α phosphorylation unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LIMK1's diverse upstream inputs (Rho-ROCK, PAK isoforms, PKA, receptor-driven dimerization) and binding-partner-imposed inhibition are integrated to produce substrate- and compartment-specific outputs remains unresolved.
  • No unified structural model of partner-regulated activation
  • Full substrate repertoire beyond cofilin and MT1-MMP undefined
  • Quantitative logic of input integration not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005856 cytoskeleton 3 GO:0005794 Golgi apparatus 1 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3
Partners
BMPR2CFL1FSCN1LATS1MMP14NTRK2PAK4PAK6

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 LIMK1 (murine Limk1) encodes a protein kinase that autophosphorylates on serine, tyrosine, and threonine residues in vitro; mutation of residue D460 within the IHRDL catalytic motif abolishes kinase activity, establishing this residue as essential for catalysis. In vitro kinase assay with GST-Limk1 fusion protein; active-site mutagenesis (D460A) Oncogene High 7478547
1995 LIMK1 (rat LIMK-1) phosphorylates serine and threonine residues of myelin basic protein in vitro, confirming serine/threonine kinase substrate activity. In vitro kinase assay with immunoprecipitated LIMK-1 and MBP as substrate Oncogene Medium 7651734
2002 LIMK-1 knockout mice show reduced cofilin phosphorylation in vivo, abnormal dendritic spine morphology, enhanced hippocampal LTP, and deficits in spatial learning and fear responses, establishing LIMK-1 as an in vivo regulator of cofilin, spine morphogenesis, and synaptic function. LIMK-1 gene knockout mouse model; electrophysiology (LTP); behavioral tests (Morris water maze, fear conditioning); immunoblotting for p-cofilin Neuron High 12123613
2003 LIMK1 physically binds the tail domain of BMPR-II (identified by yeast two-hybrid); this interaction inhibits LIMK1's ability to phosphorylate cofilin; addition of BMP4 ligand relieves this inhibition; a BMPR-II mutant with the smallest PPH-associated C-terminal truncation fails to bind or inhibit LIMK1. Yeast two-hybrid screen; co-immunoprecipitation; in vitro cofilin phosphorylation assay; truncation mutant analysis The Journal of cell biology High 12963706
2003 Fluid shear stress activates the Rho–ROCK–LIMK–cofilin pathway in vascular endothelial cells; dominant-negative forms of RhoA, ROCK, LIMK, and cofilin each block shear-stress-induced SREBP activation, placing LIMK downstream of ROCK and upstream of cofilin in this mechanosensing cascade. Dominant-negative mutant expression; reporter assays for SREBP activity; epistasis analysis in endothelial cells Circulation research Medium 12775580
2004 LIMK1 is enriched in the Golgi apparatus (requiring its LIM domain for Golgi localization) and at growth cones (requiring its PDZ domain) in neurons. Overexpression of wild-type LIMK1 suppresses trans-Golgi tubule formation and prevents Golgi fragmentation; kinase-dead LIMK1 has opposite effects. LIMK1 accelerates axon formation and regulates Golgi-derived vesicle traffic in a cofilin-phosphorylation-dependent manner. Confocal microscopy; subcellular fractionation; expression of epitope-tagged wild-type and kinase-dead LIMK1; constitutively active cofilin rescue Molecular biology of the cell High 15090620
2004 LATS1 tumor suppressor binds LIMK1 in vitro and in vivo, co-localizes with LIMK1 at the actomyosin contractile ring during cytokinesis, and inhibits LIMK1-mediated cofilin phosphorylation; loss of LATS1 increases multinucleate cells, establishing LATS1 as a negative regulator of LIMK1 during cytokinesis. GST pull-down (in vitro binding); co-immunoprecipitation; immunofluorescence co-localization; antibody microinjection; siRNA knockdown; LATS1 knockout mice Nature cell biology High 15220930
2004 LIMK1 binds BMPR-II in neurite tips; this interaction is required for BMP7-dependent induction of dendritic arbor in cortical neurons. The physical interaction of LIMK1 with BMPR-II synergizes with Cdc42 to activate LIMK1 catalytic activity, defining a Smad-independent BMP pathway that links the BMP receptor to actin dynamics during dendritogenesis. Co-immunoprecipitation; confocal colocalization; dominant-negative and kinase-dead constructs; cortical neuron dendrite morphology assays The EMBO journal High 15538389
2004 B-Raf maintains actin stress fibers in fibroblasts via a ROCKII/LIMK/cofilin pathway; B-raf−/− MEFs show reduced ROCKII expression, reduced cofilin phosphorylation, and reduced F-actin; these defects are restored by overexpression of LIMK, placing LIMK downstream of ROCKII in the B-Raf pathway. B-raf knockout mouse embryonic fibroblasts; LIMK overexpression rescue; immunoblotting for p-cofilin; F-actin staining Molecular and cellular biology Medium 15199148
2005 Alpha2-macroglobulin (alpha2M*) binding to GRP78 on prostate cancer cells activates PAK-2 (not PAK-1), which in turn phosphorylates LIMK; silencing PAK-2 gene expression greatly attenuates LIMK phosphorylation, placing PAK-2 upstream of LIMK in this signaling cascade. siRNA gene silencing; co-immunoprecipitation; in vitro kinase assay; immunoblotting for p-LIMK and p-cofilin The Journal of biological chemistry Medium 15908432
2006 LIMK1 localizes to cell–cell adhesion sites in interphase, redistributes to spindle poles during prometaphase through anaphase, and accumulates at the cleavage furrow in telophase, indicating cell-cycle-dependent spatial regulation distinct from LIMK2. Immunofluorescence analysis throughout the cell cycle; nocodazole synchronization Experimental cell research Medium 16455074
2008 In prostate cancer cells, PAK4 binds LIMK1 and phosphorylates it in an HGF-dependent manner; this interaction is concentrated in peripheral foci detected by FRET-FLIM; PAK4 and LIMK1 act synergistically to increase cell migration speed via cofilin phosphorylation. Co-immunoprecipitation; in vitro phosphorylation assay; FRET-FLIM for direct intracellular interaction; siRNA knockdown; migration assays Cellular signalling High 18424072
2009 PKA directly phosphorylates Limk1, enhancing its activity and the downstream phosphorylation of cofilin; this occurs downstream of Prkar1a loss without Rho or Rac activation, defining a Rho-independent PKA→Limk1→cofilin axis that controls cell morphology and migration. Prkar1a−/− MEFs; PKA activation by pharmacological agents; in vitro phosphorylation of Limk1 by PKA; immunoblotting; epistasis with Rho/Rac inhibitors EMBO reports High 19424295
2012 LIMK1 physically interacts with TrkB; BDNF-induced TrkB dimerization leads to LIMK1 dimerization and transphosphorylation independent of TrkB kinase activity, activating LIMK1 which then phosphorylates cofilin and promotes actin polymerization and axonal elongation. Co-immunoprecipitation; dominant-negative TrkB constructs; cofilin phosphorylation assay; membrane fractionation; axonal elongation assay The Journal of biological chemistry Medium 23086941
2012 Rho promotes a complex between fascin-1 and LIMK1/LIMK2 downstream of Rho kinase; this complex regulates filopodia stability and the interaction of fascin-1 with actin, as detected by FRET-FLIM. Co-immunoprecipitation; FRET-FLIM (fascin-1/actin interaction); Rho kinase inhibition; dominant-negative constructs BMC biology Medium 22883572
2012 Non-canonical BMPRII signaling through the LIMK/cofilin pathway mediates cadherin-6B-induced de-epithelialization during neural crest EMT; dominant-negative LIMK1 reduces de-epithelialization by cadherin-6B or BMP, and a phosphorylation-deficient cofilin mutant (S3A) inhibits de-epithelialization, placing LIMK1 and cofilin downstream of BMPRII in this process. Dominant-negative and wild-type LIMK1 overexpression in Xenopus neural tube; cofilin S3A mutant; in vivo delamination assay Developmental biology Medium 22537493
2013 DAPK functions as a scaffold protein for the LIMK/cofilin complex in TNF-induced apoptosis; TNF treatment enhances phosphorylation of LIMK at Thr508 and cofilin at Ser3; modulation of DAPK activity (inhibitor, siRNA, overexpression) correspondingly alters both phosphorylations; TNF triggers redistribution of LIMK, DAPK, and cofilin to the perinuclear compartment. Peptide array screen; siRNA knockdown; DAPK inhibitor; overexpression; immunofluorescence; immunoblotting; structural modeling The international journal of biochemistry & cell biology Medium 23702034
2014 LIMK1 interacts with adaptor LRAP25; the LRAP25-MRCK complex localizes to the lamellipodium and is required for local LIMK1 activation and cofilin phosphorylation; inhibition of MRCK or LRAP25 suppresses LIMK1 activity and disrupts lamellipodial F-actin, cell polarization, and motility. Co-immunoprecipitation; MRCK and LRAP25 siRNA knockdown; cofilin phosphorylation immunoblotting; F-actin imaging; cell migration assays The Journal of biological chemistry Medium 25107909
2015 LIMK1 interacts with and regulates the transcription factor CREB; LIMK1-KO mice are defective in late-phase LTP (L-LTP) and long-term memory (LTM) but not short-term memory; both L-LTP and LTM deficits are rescued by increasing CREB activity, identifying a LIMK1→CREB axis for LTM. LIMK1 knockout mice; co-immunoprecipitation (LIMK1-CREB interaction); electrophysiology (L-LTP); behavioral tests (LTM vs STM); CREB activator rescue Molecular and cellular biology High 25645926
2015 PAK6 binds LIMK1 and phosphorylates it at Thr-508, activating LIMK1 which then phosphorylates cofilin; PAK6 and LIMK1 co-localize in the cytoplasm; this PAK6→LIMK1→cofilin axis controls stress fiber formation and actin dynamics required for prostate cancer cell invasion. Co-immunoprecipitation; in vitro phosphorylation (PAK6→LIMK1 at Thr-508); cofilin phosphorylation immunoblotting; immunofluorescence co-localization; migration/invasion assays Oncotarget Medium 25714010
2016 LIMK1 phosphorylates tyrosine Y573 in the cytoplasmic domain of MT1-MMP, a novel non-cofilin substrate; this phosphorylation regulates cortactin association with MT1-MMP-positive endosomes and invadopodia formation, thereby controlling matrix degradation and cell invasion. Co-immunoprecipitation; in vitro kinase assay identifying Y573 phosphorylation; site-directed mutagenesis of Y573; cortactin association assay; invadopodia/matrix degradation assays; siRNA knockdown of LIMK1/2 Scientific reports High 27116935
2016 Neuroligin-1 C-terminal domain interacts with spine-associated Rap GTPase-activating protein (SPAR) and activates LIMK1/cofilin-mediated actin reorganization to enhance spine and synapse number and modulate synaptic plasticity. Co-immunoprecipitation; dominant-negative and overexpression constructs; cofilin phosphorylation assay; spine morphology and synapse density quantification; electrophysiology The Journal of cell biology Medium 26880202
2019 ROCK2 (not ROCK1) promotes dendritic spine loss via LIMK1; ROCK2-LIMK1 pathway mediates Aβ42 oligomer-induced spine degeneration and neuronal hyperexcitability; pharmacological inhibition of LIMK1 renders dendritic spines resilient to Aβ42 and rescues spine loss in hAPP mice. Primary hippocampal neuron cultures; ROCK1/ROCK2 overexpression; LIMK1 pharmacological inhibition; live-cell microscopy; multielectrode array; hAPP mouse model with LIMK1 inhibitor treatment Science signaling High 31239325
2019 Nischarin mutation (L972P) in edison mice activates PAK1, RAC1, and downstream LIMK1 and NF-κB signaling in middle ear epithelia, contributing to chronic otitis media, establishing LIMK1 as part of the Nischarin/PAK1/RAC1 pathway in middle ear inflammation. N-ethyl-N-nitrosourea mutagenesis mouse model; genetic interaction analysis (Nisch × Itga5); signaling pathway analysis in middle ear epithelia; immunoblotting PLoS genetics Medium 28806779
2019 ROCK1 (not LIMK1 or PAK2) is the key non-redundant regulator of apoptotic membrane blebbing and apoptotic body formation; CRISPR/Cas9 deletion of LIMK1 does not impair apoptotic blebbing, demonstrating that LIMK1 is dispensable for this process. CRISPR/Cas9 knockout of LIMK1, ROCK1, PAK2; pharmacological inhibition; apoptotic blebbing quantification; apoptotic body formation assay Cell death and differentiation High 31043701
2019 X-ray crystal structures of the LIMK1 kinase domain reveal a unique 'rock-and-poke' catalytic mechanism, the basis of substrate specificity, and regulation by activation loop phosphorylation; crystal structures with inhibitors PF-477736 and staurosporine provide insight into LIMK1 plasticity upon ligand binding. X-ray crystallography; RapidFire mass spectrometry activity assay; differential scanning fluorimetry; mutagenesis The Biochemical journal High 31652302
2009 LIMK1 acts downstream of BMPR-II in extending retinal ganglion cell (RGC) axons: expression of a BMPRII lacking the LIMK1-binding domain dramatically shortens axons, but manipulation of LIMK1 activity did not alter dendrite growth in the same neurons, demonstrating compartment-specific LIMK1 regulation by BMPRII. In vivo Xenopus RGC experiments; wild-type and kinase-dead LIMK1 expression; BMPRII truncation mutant expression; axon and dendrite length quantification Developmental biology Medium 19361494
2013 Delta opioid receptor and ORL1 receptor agonists activate cofilin through a ROCK–LIMK–β-arrestin-1 pathway to regulate actin polymerization; this controls receptor function (inhibition of voltage-dependent Ca2+ channels in DRG neurons); behavioral effects of these agonists are enhanced in β-arrestin-1 knockout mice or prevented by ROCK inhibition. DRG neuron electrophysiology; β-arrestin-1 knockout mice; ROCK inhibitor (Y-27632); cofilin activation assay; behavioral assays Cell reports Medium 24239352
2014 LIMK-dependent actin polymerization in DRG primary sensory neurons promotes inflammatory heat hyperalgesia; inflammatory stimuli increase LIMK activity and cofilin phosphorylation in DRG; LIMK knockdown or prevention of cofilin phosphorylation attenuates hyperalgesia and blocks inflammatory enhancement of TRPV1 response and serine phosphorylation of TRPV1. In vivo rat CFA model; LIMK knockdown; cofilin phosphorylation assay; actin polymerization assay; TRPV1 electrophysiology; behavioral pain assays Science signaling High 24962708
2018 RhoA regulates the LIMK1/2-cofilin pathway during mouse oocyte meiosis: ROCK inhibition decreases p-LIMK1/2 and p-cofilin; LIMK1/2 disruption impairs spindle migration, polar body extrusion, and actin filament distribution; the pathway is ordered as RhoA→ROCK→LIMK1/2→cofilin. Mouse oocyte live-cell imaging; LIMK1/LIMK2 knockdown; ROCK inhibition; RhoA inhibition; cofilin phosphorylation immunoblotting; spindle morphology analysis Journal of cellular physiology Medium 29319181
2020 LIMK1 mRNA stability is increased when the m6A reader YTHDC2 is downregulated, because YTHDC2 normally recognizes the GGACA m6A site on LIMK1 mRNA and promotes its degradation; elevated LIMK1 then facilitates eIF2α phosphorylation, ER stress, and stress granule formation, causing 5-FU chemoresistance. YTHDC2 siRNA knockdown; m6A site mutation; LIMK1 mRNA stability assay; eIF2α phosphorylation immunoblotting; stress granule immunofluorescence; 5-FU sensitivity assays Cancer letters Medium 37778684
2021 High NRG1 expression activates LIMK1 and increases cofilin phosphorylation in postsynaptic densities; inhibiting LIMK1 or blocking the NRG1-LIMK1 interaction rescues spine density reduction in ctoNrg1 mice overexpressing neuregulin-1. NRG1-overexpressing transgenic mice; LIMK1 inhibitor treatment; NRG1-LIMK1 interaction blocking; immunoblotting for p-cofilin; spine density quantification; mEPSC electrophysiology Cell death & disease Medium 33854034

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron 551 12123613
2003 Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1. The Journal of cell biology 268 12963706
2004 Activation of LIMK1 by binding to the BMP receptor, BMPRII, regulates BMP-dependent dendritogenesis. The EMBO journal 180 15538389
2004 LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1. Nature cell biology 154 15220930
2005 Binding of activated alpha2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK. The Journal of biological chemistry 152 15908432
2008 A PAK4-LIMK1 pathway drives prostate cancer cell migration downstream of HGF. Cellular signalling 123 18424072
2004 LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons. Molecular biology of the cell 111 15090620
2003 Rho-ROCK-LIMK-cofilin pathway regulates shear stress activation of sterol regulatory element binding proteins. Circulation research 105 12775580
1995 Limk1 is predominantly expressed in neural tissues and phosphorylates serine, threonine and tyrosine residues in vitro. Oncogene 102 7478547
2019 Targeting ROCK/LIMK/cofilin signaling pathway in cancer. Archives of pharmacal research 87 31030376
2004 B-Raf acts via the ROCKII/LIMK/cofilin pathway to maintain actin stress fibers in fibroblasts. Molecular and cellular biology 87 15199148
1995 LIMK-1 and LIMK-2, two members of a LIM motif-containing protein kinase family. Oncogene 86 7651734
2003 Sertoli-germ cell adherens junction dynamics in the testis are regulated by RhoB GTPase via the ROCK/LIMK signaling pathway. Biology of reproduction 85 12606349
2009 LIMK1 and LIMK2 are important for metastatic behavior and tumor cell-induced angiogenesis of pancreatic cancer cells. Zebrafish 82 20047470
2016 Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization. The Journal of cell biology 81 26880202
2003 Regulation of spine morphology and synaptic function by LIMK and the actin cytoskeleton. Reviews in the neurosciences 81 14513866
2019 DANCR promotes HCC progression and regulates EMT by sponging miR-27a-3p via ROCK1/LIMK1/COFILIN1 pathway. Cell proliferation 76 31038266
2019 Pharmacologic inhibition of LIMK1 provides dendritic spine resilience against β-amyloid. Science signaling 75 31239325
2014 MiR-27b targets LIMK1 to inhibit growth and invasion of NSCLC cells. Molecular and cellular biochemistry 69 24390089
2015 Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway. Oncotarget 67 25714010
2004 LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome. BioEssays : news and reviews in molecular, cellular and developmental biology 67 14745832
2016 LIMK Regulates Tumor-Cell Invasion and Matrix Degradation Through Tyrosine Phosphorylation of MT1-MMP. Scientific reports 63 27116935
2009 Regulation of actin function by protein kinase A-mediated phosphorylation of Limk1. EMBO reports 63 19424295
2019 ROCK1 but not LIMK1 or PAK2 is a key regulator of apoptotic membrane blebbing and cell disassembly. Cell death and differentiation 61 31043701
2015 LIMK1 regulates long-term memory and synaptic plasticity via the transcriptional factor CREB. Molecular and cellular biology 59 25645926
2009 DGCR6L, a novel PAK4 interaction protein, regulates PAK4-mediated migration of human gastric cancer cell via LIMK1. The international journal of biochemistry & cell biology 59 19778628
2020 Exosomal lncRNA H19 promotes the progression of hepatocellular carcinoma treated with Propofol via miR-520a-3p/LIMK1 axis. Cancer medicine 58 32767662
2017 Electroacupuncture Regulates Hippocampal Synaptic Plasticity via miR-134-Mediated LIMK1 Function in Rats with Ischemic Stroke. Neural plasticity 56 28116173
2011 Nuclear and cytoplasmic LIMK1 enhances human breast cancer progression. Molecular cancer 56 21682918
2016 Diallyl disulfide suppresses epithelial-mesenchymal transition, invasion and proliferation by downregulation of LIMK1 in gastric cancer. Oncotarget 55 26871290
2021 Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo. Journal of cellular and molecular medicine 54 33982869
2019 MiR-128-3p suppresses breast cancer cellular progression via targeting LIMK1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 54 31078043
2012 DADS downregulates the Rac1-ROCK1/PAK1-LIMK1-ADF/cofilin signaling pathway, inhibiting cell migration and invasion. Oncology reports 53 23233092
2021 Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling. Cell death & disease 52 33414429
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
2006 A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and confers susceptibility to intracranial aneurysms. Human molecular genetics 48 16611674
1995 The murine LIM-kinase gene (limk) encodes a novel serine threonine kinase expressed predominantly in trophoblast giant cells and the developing nervous system. Mechanisms of development 48 8541208
2019 Baicalin regulates depression behavior in mice exposed to chronic mild stress via the Rac/LIMK/cofilin pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 47 31176122
2023 LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features. Cells 46 36899941
2017 Downregulation of LIMK1-ADF/cofilin by DADS inhibits the migration and invasion of colon cancer. Scientific reports 46 28358024
2014 miR-143 inhibits NSCLC cell growth and metastasis by targeting Limk1. International journal of molecular sciences 45 25003638
2013 Select G-protein-coupled receptors modulate agonist-induced signaling via a ROCK, LIMK, and β-arrestin 1 pathway. Cell reports 44 24239352
2012 A novel Rho-dependent pathway that drives interaction of fascin-1 with p-Lin-11/Isl-1/Mec-3 kinase (LIMK) 1/2 to promote fascin-1/actin binding and filopodia stability. BMC biology 43 22883572
2015 Bis-aryl urea derivatives as potent and selective LIM kinase (Limk) inhibitors. Journal of medicinal chemistry 42 25621531
2018 LIMK/cofilin pathway and Slingshot are implicated in human colorectal cancer progression and chemoresistance. Virchows Archiv : an international journal of pathology 40 29352327
2021 LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target. Oncogene 39 33883692
2018 Recombinant human BMP-2 accelerates the migration of bone marrow mesenchymal stem cells via the CDC42/PAK1/LIMK1 pathway in vitro and in vivo. Biomaterials science 39 30484785
2023 LIMK1 m6A-RNA methylation recognized by YTHDC2 induces 5-FU chemoresistance in colorectal cancer via endoplasmic reticulum stress and stress granule formation. Cancer letters 38 37778684
1999 Identification and characterization of TESK2, a novel member of the LIMK/TESK family of protein kinases, predominantly expressed in testis. Genomics 38 10512679
2014 MiR-20a inhibits cutaneous squamous cell carcinoma metastasis and proliferation by directly targeting LIMK1. Cancer biology & therapy 37 25019203
2006 Different activity regulation and subcellular localization of LIMK1 and LIMK2 during cell cycle transition. Experimental cell research 37 16455074
2021 SphK2/S1P Promotes Metastasis of Triple-Negative Breast Cancer Through the PAK1/LIMK1/Cofilin1 Signaling Pathway. Frontiers in molecular biosciences 34 33968977
2019 GPER stabilizes F-actin cytoskeleton and activates TAZ via PLCβ-PKC and Rho/ROCK-LIMK-Cofilin pathway. Biochemical and biophysical research communications 34 31277940
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
2020 LIMK (LIM Kinase) Inhibition Prevents Vasoconstriction- and Hypertension-Induced Arterial Stiffening and Remodeling. Hypertension (Dallas, Tex. : 1979) 33 32594801
2020 Dasatinib Inhibits Lung Cancer Cell Growth and Patient Derived Tumor Growth in Mice by Targeting LIMK1. Frontiers in cell and developmental biology 33 33344441
2014 Overexpression of LIMK1 promotes tumor growth and metastasis in gastric cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 33 25661344
2010 Differing contributions of LIMK and ROCK to TGFβ-induced transcription, motility and invasion. European journal of cell biology 31 21074289
2014 EBP50 inhibits the migration and invasion of human breast cancer cells via LIMK/cofilin and the PI3K/Akt/mTOR/MMP signaling pathway. Medical oncology (Northwood, London, England) 30 25119502
2013 Downregulation of LIMK1 level inhibits migration of lung cancer cells and enhances sensitivity to chemotherapy drugs. Oncology research 30 24063279
2012 Pak1/LIMK1/Cofilin Pathway Contributes to Tumor Migration and Invasion in Human Non-Small Cell Lung Carcinomas and Cell Lines. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 30 22802696
2012 LIM kinase 1 (LIMK1) interacts with tropomyosin-related kinase B (TrkB) and Mediates brain-derived neurotrophic factor (BDNF)-induced axonal elongation. The Journal of biological chemistry 30 23086941
2021 Long non-coding RNA Lnc-408 promotes invasion and metastasis of breast cancer cell by regulating LIMK1. Oncogene 29 34079084
2020 DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway. OncoTargets and therapy 29 32110046
2019 Actin Dynamics, Regulated by RhoA-LIMK-Cofilin Signaling, Mediates Rod Photoreceptor Axonal Retraction After Retinal Injury. Investigative ophthalmology & visual science 29 31112612
2017 A mutation in Nischarin causes otitis media via LIMK1 and NF-κB pathways. PLoS genetics 29 28806779
2012 Cadherin-6B stimulates an epithelial mesenchymal transition and the delamination of cells from the neural ectoderm via LIMK/cofilin mediated non-canonical BMP receptor signaling. Developmental biology 28 22537493
2010 Coagulation Factor Xa inhibits cancer cell migration via LIMK1-mediated cofilin inactivation. Thrombosis research 28 20347121
2021 IP-10 Promotes Latent HIV Infection in Resting Memory CD4+ T Cells via LIMK-Cofilin Pathway. Frontiers in immunology 27 34447368
2013 ECM-dependent HIF induction directs trophoblast stem cell fate via LIMK1-mediated cytoskeletal rearrangement. PloS one 27 23437279
2022 Structural Aspects of LIMK Regulation and Pharmacology. Cells 26 35011704
2019 Nonconserved miR-608 suppresses prostate cancer progression through RAC2/PAK4/LIMK1 and BCL2L1/caspase-3 pathways by targeting the 3'-UTRs of RAC2/BCL2L1 and the coding region of PAK4. Cancer medicine 26 31389670
2016 Simvastatin Attenuates Neuropathic Pain by Inhibiting the RhoA/LIMK/Cofilin Pathway. Neurochemical research 26 27216618
2021 Spine impairment in mice high-expressing neuregulin 1 due to LIMK1 activation. Cell death & disease 25 33854034
2019 Rho-Associated Protein Kinase (ROCK) Promotes Proliferation and Migration of PC-3 and DU145 Prostate Cancer Cells by Targeting LIM Kinase 1 (LIMK1) and Matrix Metalloproteinase-2 (MMP-2). Medical science monitor : international medical journal of experimental and clinical research 25 31026254
2015 Design, synthesis and biological characterization of selective LIMK inhibitors. Bioorganic & medicinal chemistry letters 25 26233434
2000 Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23. Mammalian genome : official journal of the International Mammalian Genome Society 25 11003705
2020 Cofilin Inhibition by Limk1 Reduces Rod Formation and Cell Apoptosis after Ischemic Stroke. Neuroscience 24 32697981
2019 Lessons from LIMK1 enzymology and their impact on inhibitor design. The Biochemical journal 24 31652302
2014 LIMK-dependent actin polymerization in primary sensory neurons promotes the development of inflammatory heat hyperalgesia in rats. Science signaling 24 24962708
2004 CD29 integrin- and LIMK1/cofilin-mediated actin reorganization regulates the migration of haematopoietic progenitor cells underneath bone marrow stromal cells. Genes to cells : devoted to molecular & cellular mechanisms 24 15066125
2020 Effects of PAK4/LIMK1/Cofilin-1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells. Journal of clinical laboratory analysis 23 32463132
2020 Knockdown of RhoGDI2 represses human gastric cancer cell proliferation, invasion and drug resistance via the Rac1/Pak1/LIMK1 pathway. Cancer letters 23 32860848
2016 Sevoflurane induces cognitive impairments via the MiR-27b/LIMK1-signaling pathway in developing rats. Inhalation toxicology 23 27973945
2019 LIMK1 and LIMK2 regulate cortical development through affecting neural progenitor cell proliferation and migration. Molecular brain 22 31319858
2018 The small GTPase RhoA regulates the LIMK1/2-cofilin pathway to modulate cytoskeletal dynamics in oocyte meiosis. Journal of cellular physiology 22 29319181
2014 Adaptor protein LRAP25 mediates myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) regulation of LIMK1 protein in lamellipodial F-actin dynamics. The Journal of biological chemistry 22 25107909
2013 Identification of DAPK as a scaffold protein for the LIMK/cofilin complex in TNF-induced apoptosis. The international journal of biochemistry & cell biology 21 23702034
2002 Head, neck, and spines: a role for LIMK-1 in the hippocampus. Neuron 21 12123600
2020 Downregulation of Rac1/PAK1/LIMK1/cofilin signaling pathway in colon cancer SW620 cells treated with Chlorin e6 photodynamic therapy. Photodiagnosis and photodynamic therapy 20 33307230
2011 Overexpression of LIMK1 promotes migration ability of multidrug-resistant osteosarcoma cells. Oncology research 20 22715593
2009 LIMK1 acts downstream of BMP signaling in developing retinal ganglion cell axons but not dendrites. Developmental biology 20 19361494
2021 LncRNA Rian ameliorates sevoflurane anesthesia-induced cognitive dysfunction through regulation of miR-143-3p/LIMK1 axis. Human cell 19 33616869
2021 FOXD3‑AS1/miR‑128‑3p/LIMK1 axis regulates cervical cancer progression. Oncology reports 19 33760158
2020 Diallyl disulfide induces downregulation and inactivation of cofilin 1 differentiation via the Rac1/ROCK1/LIMK1 pathway in leukemia cells. International journal of oncology 19 32124958
2020 Up-regulation of LIMK1 expression in prostate cancer is correlated with poor pathological features, lymph node metastases and biochemical recurrence. Journal of cellular and molecular medicine 19 32168432
2019 Deletion of Limk1 and Limk2 in mice does not alter cochlear development or auditory function. Scientific reports 19 30833597
2017 Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction. Molecular neurobiology 19 28084590
2016 MicroRNA-138 inhibits migration and invasion of non-small cell lung cancer cells by targeting LIMK1. Molecular medicine reports 19 27665963
2014 Multimodal effects of small molecule ROCK and LIMK inhibitors on mitosis, and their implication as anti-leukemia agents. PloS one 19 24642638

Missed literature

Know a paper Affinage missed for LIMK1? Flag it for the maintainers and the community.

No submissions yet.