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Showing MYLK — SMMLCK is a alias.

MYLK

Myosin light chain kinase, smooth muscle · UniProt Q15746

Length
1914 aa
Mass
210.7 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYLK is a single gene that produces multiple functionally distinct products—smooth muscle and nonmuscle myosin light chain kinase isoforms (220-kDa and 130-kDa smMLCK, nonmuscle MLCK1–4) and the non-catalytic C-terminal fragment telokin—through alternative promoters and splicing, thereby controlling actomyosin contractility across smooth muscle contraction, epithelial barrier function, and cell motility (PMID:10198165, PMID:16774989). The kinase isoforms phosphorylate the myosin II regulatory light chain to organize F-actin and drive contraction, migration, and epithelial-mesenchymal transition (PMID:29855744), and their enzymatic activation depends on regulatory phosphorylation (e.g., S1P-induced Y464) that, when impaired by coding variants, attenuates peripheral translocation and lamellipodial protrusion (PMID:29480069). Telokin is transcribed from an intronic, smooth-muscle-specific promoter as a protein identical to the smMLCK C-terminus, folds as an immunoglobulin-like beta-barrel, and acts as a relaxant modulator that induces Ca2+ desensitization by activating myosin light chain phosphatase (PMID:1748667, PMID:1404391, PMID:9556631); mechanistically, phospho-telokin (Ser-13) binds inhibited phospho-MYPT1 directly, facilitating phosphatase engagement of phosphomyosin and accelerating MLC dephosphorylation, with PKA/PKG phosphorylation at Ser-13 potentiating this effect (PMID:11346659, PMID:22544752). Telokin-null mice confirm this physiological role through reduced phosphatase activity and increased Ca2+ sensitivity that is rescued by recombinant telokin (PMID:16461919). The MLCK1 splice isoform is uniquely targeted to the perijunctional actomyosin ring by an isoform-specific domain, and this recruitment—blockable by the small molecule divertin without inhibiting catalysis—is required for cytokine-induced tight junction permeability loss (PMID:15507455, PMID:30936544). MYLK expression is induced via TLR4/MyD88/TAK-1/NF-κB signaling and tuned post-transcriptionally by m6A machinery and miRNAs (PMID:30711488, PMID:36170767, PMID:38196046, PMID:39013850). Loss-of-function MYLK missense variants that reduce kinase activity cause heritable thoracic aortic aneurysm and dissection (PMID:29925964, PMID:29544503).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1991 High

    Established that telokin is not a separate gene but the independently transcribed C-terminal domain of smMLCK, defining the multi-product architecture of the locus.

    Evidence cDNA/genomic cloning and promoter mapping with Northern blot

    PMID:1748667

    Open questions at the time
    • Did not define telokin's biochemical function
    • Did not enumerate the full set of gene products
  2. 1992 High

    Resolved telokin's fold as an immunoglobulin-like beta-barrel, providing the structural basis for its protein-interaction modulatory role.

    Evidence X-ray crystallography at 2.8 Å

    PMID:1404391

    Open questions at the time
    • Structure alone did not assign binding partners or function
  3. 1996 High

    Showed telokin expression is smooth-muscle-specific and driven by an intronic promoter, distinguishing it from the kinase isoforms.

    Evidence Western/Northern blot, reporter assays, transgenic mice

    PMID:8764148

    Open questions at the time
    • Did not identify the transcription factors driving specificity
  4. 1997 Medium

    Identified telokin's biochemical activity as a modulator of smMLCK oligomeric state and a substrate of smMLCK itself, linking telokin to kinase regulation.

    Evidence In vitro phosphorylation, sedimentation, kinase assays

    PMID:9078244 PMID:9371697

    Open questions at the time
    • In vitro reconstitution did not establish physiological relevance
    • Threonine phosphorylation site not mapped to residue
  5. 1998 High

    Defined telokin's core physiological function as inducing Ca2+ desensitization by enhancing myosin light chain phosphatase activity, potentiated by PKA/PKG phosphorylation.

    Evidence Permeabilized smooth muscle with recombinant protein and force measurements

    PMID:9556631

    Open questions at the time
    • Molecular target of telokin within the phosphatase complex unknown
    • Phosphorylation site not yet identified
  6. 2000 High

    Mapped Ser-13 as the primary in vivo cyclic-nucleotide-dependent phosphorylation site, providing the molecular handle for telokin's relaxant regulation.

    Evidence In vivo 32P-labeling, phosphopeptide mapping, site-directed mutagenesis

    PMID:10981712

    Open questions at the time
    • Functional consequence of Ser-13 phosphorylation not yet demonstrated
  7. 2001 High

    Demonstrated that Ser-13 phosphorylation (mimicked by S13D) enhances telokin's Ca2+-desensitizing activity, linking the phosphosite to function.

    Evidence Phosphomimetic mutants in permeabilized smooth muscle force assays

    PMID:11346659

    Open questions at the time
    • Did not identify the phosphatase subunit telokin engages
  8. 1999 High

    Established that smooth muscle and nonmuscle MLCK isoforms arise from a single MYLK gene by alternative splicing, defining the isoform repertoire.

    Evidence cDNA cloning, genomic analysis, RT-PCR, Northern blot

    PMID:10198165

    Open questions at the time
    • Functional distinctions among nonmuscle isoforms not resolved
  9. 2006 High

    Genetic knockout proved telokin's in vivo role in maintaining phosphatase activity and Ca2+ desensitization, with recombinant rescue confirming causality.

    Evidence Telokin knockout mice, phosphatase and Ca2+-force assays, recombinant rescue

    PMID:16461919

    Open questions at the time
    • Direct phosphatase-binding mechanism still unresolved at this stage
  10. 2004 High

    Localized the MLCK1 long splice isoform to the perijunctional actomyosin ring and linked it functionally to tight junction permeability regulation.

    Evidence Immunolocalization, siRNA knockdown, transepithelial resistance

    PMID:15507455

    Open questions at the time
    • Targeting determinant for PAMR recruitment not yet identified
  11. 2012 High

    Resolved the molecular mechanism of telokin action: phospho-telokin directly binds inhibited phospho-MYPT1 to facilitate phosphatase engagement of phosphomyosin.

    Evidence GST pulldown, surface plasmon resonance, protein ligation assay, KO muscle reconstitution

    PMID:22544752

    Open questions at the time
    • Structural basis of the telokin–MYPT1 interaction not solved
  12. 2019 High

    Identified an isoform-unique domain that recruits MLCK1 to the perijunctional actomyosin ring and showed this recruitment, not catalysis, mediates cytokine-induced barrier loss—targetable by divertin.

    Evidence Domain mutagenesis, small molecule screen, live imaging, mouse barrier/IBD models

    PMID:30936544

    Open questions at the time
    • Binding partner of the recruitment domain at the PAMR not defined
  13. 2018 Medium

    Established MYLK as a heritable thoracic aortic disease gene through loss-of-function missense variants that reduce kinase activity.

    Evidence Kinase assays on purified variant proteins and clinical cohort/family analysis

    PMID:29544503 PMID:29925964

    Open questions at the time
    • Functional assays fail to classify all pathogenic variants
    • Vascular mechanism downstream of reduced kinase activity not detailed
  14. 2022 Medium

    Showed MYLK is itself a kinase substrate, phosphorylated by SIK2 at Ser343 to drive MYL2 phosphorylation and cancer cell motility, expanding upstream regulation.

    Evidence In vitro kinase assay, phosphosite identification, migration/metastasis assays

    PMID:35278271

    Open questions at the time
    • Single lab
    • Generality of Ser343 regulation across isoforms unknown
  15. 2024 Medium

    Defined post-transcriptional control of MYLK by m6A machinery and miRNAs governing vascular smooth muscle phenotype and stem-cell differentiation.

    Evidence m6A-RIP, mRNA stability, miRNA target validation, rescue in mouse models

    PMID:36170767 PMID:38196046 PMID:39013850

    Open questions at the time
    • Whether these regulators act on specific MYLK isoforms not resolved
    • Single-lab studies per regulator

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct MYLK isoforms are differentially deployed and regulated across smooth muscle, endothelium, epithelium, and cancer to produce tissue-specific contractile and barrier outcomes remains unresolved.
  • No unified structural model of isoform-specific targeting domains
  • Endogenous binding partners of the MLCK1 recruitment domain unknown
  • Isoform-resolved contributions to disease phenotypes not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 3 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-397014 Muscle contraction 3
Partners
14-3-3CALMODULINHNRNPA1IGF2BP3METTL3MYPT1SIK2

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Telokin is the independently expressed C-terminal domain of smooth muscle MLCK, transcribed from a promoter located within an intron of the MLCK gene (in the 3' region encoding the calmodulin-binding domain), producing a protein identical to the last 155 residues of smMLCK. cDNA/genomic cloning, promoter mapping, Northern blot The Journal of biological chemistry High 1748667
1992 The three-dimensional structure of telokin (C-terminal domain of smMLCK) at 2.8 Å resolution reveals seven strands of antiparallel beta-pleated sheet forming an immunoglobulin-like beta-barrel fold, structurally homologous to immunoglobulin constant domain CH2. X-ray crystallography Journal of molecular biology High 1404391
1996 Telokin protein and mRNA are expressed exclusively in smooth muscle tissues and cells (not in non-muscle cells), driven by a smooth muscle cell-specific promoter located within an intron of the smMLCK gene; transgenic mice confirmed this tissue specificity in vivo. Western blot, Northern blot, in vitro transfection reporter assays, transgenic mice with SV40 T-antigen reporter The American journal of physiology High 8764148
1997 Serum response factor (SRF) binding to a CArG element proximal to the TATA sequence is required for high levels of telokin transcription in A10 smooth muscle cells; MEF2 binds the AT-rich region but is not required for activity. Luciferase reporter gene assays, gel mobility shift assays, deletion/mutation analysis The American journal of physiology Medium 9142867
1997 Telokin modulates the oligomeric state of smMLCK: it solubilizes large MLCK oligomers, shifts the distribution toward dimers, and reduces MLCK binding to filamentous myosin, thereby inhibiting phosphorylation of regulatory light chain in filamentous myosin substrates but not isolated light chain. In vitro phosphorylation assays, sedimentation, biochemical fractionation The Biochemical journal Medium 9078244
1997 Telokin is phosphorylated by smMLCK itself (at a threonine residue, up to 0.25 mol/mol stoichiometry) in a Ca2+/calmodulin-dependent manner; this phosphorylation modulates kinase oligomer interactions with telokin and affects MLCK activity. In vitro kinase assay, enzyme kinetics The Biochemical journal Medium 9371697
1998 Telokin induces Ca2+ desensitization in smooth muscle by enhancing myosin light chain phosphatase (MLCP) activity, accelerating MLC dephosphorylation and relaxation; phosphorylation of telokin by cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) potentiates this relaxant effect. Permeabilized smooth muscle preparations, recombinant protein, phosphorylation assays, force measurements The Journal of biological chemistry High 9556631
1998 A 310-bp promoter fragment (-163 to +147) is sufficient for smooth muscle cell-specific telokin expression in vivo; a distal estrogen response element (ERE) between -1447 and -1474 is additionally required for expression in uterine smooth muscle. Transgenic mice with reporter gene, luciferase assays, estrogen stimulation The American journal of physiology Medium 9612204
1999 A single human MYLK gene produces both smooth muscle and nonmuscle MLCK isoforms through alternative splicing of a single pre-mRNA precursor, yielding at least five nonmuscle isoforms (MLCK1–4); MLCK2 is the dominant nonmuscle splice variant expressed in human tissues. cDNA cloning, genomic analysis, RT-PCR, Northern blot Genomics High 10198165
2000 Telokin is phosphorylated in vivo at Ser-13 (the primary site) upon forskolin stimulation in rabbit ileum; portal vein telokin is phosphorylated at both Ser-13 and Ser-19 in vivo. Ser-13 mutation (to Ala) abolishes in vitro phosphorylation by cyclic nucleotide-dependent kinases. In vivo 32P-labeling with forskolin/GTPγS stimulation, phosphopeptide mapping, site-directed mutagenesis, in vitro kinase assays FEBS letters High 10981712
2001 Phosphorylation of telokin at Ser-13 (mimicked by S13D mutant) enhances its Ca2+-desensitizing activity in smooth muscle; the S13D mutant is more effective than wild-type, and its effect is not further enhanced by 8-Br-cGMP confirming Ser-13 specificity. The S19A mutant is more effective than wild-type, while S19D is not different. The C-terminal acidic tail (residues 142–155) is not required for relaxant activity. Site-directed mutagenesis, permeabilized smooth muscle force measurements, recombinant protein The Journal of biological chemistry High 11346659
2001 Telokin mRNA expression is restricted to smooth muscle cell layers in adult and embryonic tissues; expression is first detected in mouse gut at embryonic day 11.5 and is absent from cardiac or skeletal muscle; telokin protein expression increases postnatally in male and female reproductive tract smooth muscle. In situ mRNA hybridization, Western blot, postnatal developmental analysis American journal of physiology. Cell physiology Medium 11121372
2002 Telokin translocates from cytosol to near the plasma membrane in living smooth muscle cells in response to cGMP signaling (sodium nitroprusside or 8-Br-cGMP); this translocation requires phosphorylation at Ser-13 and/or Ser-19 and is dependent on both PKG and MAPK activity. GFP-tagged telokin live imaging in primary cultured smooth muscle cells, pharmacological inhibitors, phosphorylation site mutants American journal of physiology. Cell physiology Medium 12176732
2004 The MLCK1 splice isoform (long MLCK) localizes specifically to the perijunctional actomyosin ring in well-differentiated intestinal absorptive enterocytes; siRNA knockdown of MLCK1 specifically reduces tight junction permeability during Na+-glucose cotransport-dependent regulation. Immunolocalization, siRNA knockdown, transepithelial resistance measurement, crypt-villus expression analysis The Journal of biological chemistry High 15507455
2004 Thyrotroph embryonic factor (TEF) binds to the AT-rich region of the telokin promoter and specifically activates telokin gene transcription in a calcium-dependent manner in smooth muscle cells; TEF does not activate SM22α, smooth muscle α-actin, or smooth muscle myosin heavy chain promoters. Southwestern screen, gel mobility shift assay, luciferase reporter assays, adenoviral overexpression in A10 cells The Journal of biological chemistry Medium 14702338
2005 Telokin mediates Ca2+ desensitization by activating myosin light chain phosphatase (MLCP) in both phasic (ileum) and tonic (femoral artery) smooth muscle; the phospho-telokin mimetic S13D is more effective than wild-type; the extent of relaxation correlates with relative telokin content (27 μM in ileum vs 6 μM in femoral artery). Alpha-toxin permeabilized smooth muscle, caged-ATP photolysis, recombinant telokin (S13D mutant), force measurements Journal of muscle research and cell motility Medium 15750850
2006 Telokin null mice show ~30% decreased MLCP activity in ileal smooth muscle, increased Ca2+ sensitivity of force (leftward shift of Ca2+-force relationship), increased MLC phosphorylation, and ~50% attenuation of 8-Br-cGMP-induced Ca2+ desensitization; these effects are rescued by recombinant telokin. No difference was observed in aorta (low telokin content). Telokin knockout mice (congenic background), myosin light chain phosphatase activity assay, Ca2+-force relationship, permeabilized muscle force measurements, recombinant protein rescue Proceedings of the National Academy of Sciences of the United States of America High 16461919
2006 The 130-kDa smMLCK isoform is transcribed from an internal CArG-dependent promoter within the mouse mylk gene; SRF binds to a CArG box at -167 to -151 both in vitro and in vivo (by ChIP); SRF knockdown reduces endogenous smMLCK expression; GATA-6 binding to a consensus GATA site inhibits smMLCK promoter activity and blocks myocardin-induced expression. Luciferase reporter assays, gel mobility shift assay, ChIP, siRNA knockdown, promoter deletion analysis American journal of physiology. Cell physiology Medium 16407417
2006 The mylk1 gene encodes at least four protein products (two 220-kDa MLCK isoforms, 130-kDa MLCK, and telokin) from four independent promoters; these kinase products regulate nonmuscle and smooth muscle myosin II activity, controlling contractile processes including smooth muscle contraction, cell adhesion, migration, and proliferation. Review synthesizing promoter and expression studies American journal of physiology. Cell physiology Medium 16774989
2012 Phospho-telokin (S13D) activates myosin light chain phosphatase by directly interacting with and binding to inhibited phospho-MYPT1 (regulatory subunit of MLCP), facilitating its binding to phosphomyosin and accelerating MLC20 dephosphorylation; this mechanism does not involve changes in MYPT1 phosphorylation status at Thr-696/Thr-853 or Rho kinase activity. GST-MYPT1 pulldown, surface plasmon resonance, protein ligation assay, telokin-null mouse smooth muscle reconstitution, phosphatase activity assays The Journal of biological chemistry High 22544752
2015 MYLK (MLCK) is identified as a novel target of miR-200c regulated by the ZEB1/miR-200 feedback loop; depletion of MYLK in breast cancer cells reduces invasion and invadopodia formation, identifying MYLK as a player in invadopodia formation downstream of ZEB1/EMT signaling. In silico screening, miR-200c target validation, siRNA knockdown, invasion/invadopodia assays Oncotarget Medium 26334100
2015 Conditional oocyte-specific knockout of Mylk1 in mice causes subfertility with delayed morula-to-blastocyst transition (>1/3 embryos at morula at 3.5 dpc), while oocyte meiotic maturation, spindle organization, polarity establishment, and polar body extrusion are unaffected. Cre-loxP conditional knockout, embryo developmental staging in vivo and in vitro Biology of reproduction Medium 25761595
2015 NMR spectroscopy and molecular modeling of the nmMLCK N-terminal domain show that disease-associated MYLK SNPs (P21H, S147P, V261A) localize to loops connecting immunoglobulin-like domains and adversely affect a 14-3-3 protein-protein interaction motif; 14-3-3 binding was confirmed by immunoprecipitation. 1H-15N HSQC NMR spectroscopy, molecular modeling, immunoprecipitation/Western blot PloS one Medium 26111161
2017 Mechanical stress (18% cyclic stretch) increases nmMLCK2 splice variant expression in human lung endothelial cells; MYLK SNPs rs77323602 and rs147245669 alter exon 11 donor/acceptor sites to regulate alternative splicing, with rs147245669 favoring nmMLCK2 production; the splicing factor hnRNPA1 directly regulates MYLK exon 11 splicing. Minigene constructs, RT-PCR, cyclic stretch model, lymphoblastoid cell line validation, gel shift assay American journal of respiratory cell and molecular biology Medium 27529643 29077485
2018 Disease-associated MYLK coding SNPs (Pro21His, Ser147Pro, Val261Ala) reduce S1P-induced phosphorylation at Y464 (key regulatory site for nmMLCK enzymatic activation), attenuate nmMLCK translocation to the cell periphery, and retard S1P-induced lamellipodial protrusion in human lung endothelial cells. Cell immunofluorescence assays, kymographic assays, MYLK transgene expression with SNP variants Pulmonary circulation Medium 29480069
2018 MYLK missense variants associated with familial thoracic aortic disease decrease MLCK kinase activity; loss-of-function MYLK variants cause heritable thoracic aortic dissection. Functional kinase assays demonstrated that at least one missense variant reduces kinase activity, though functional assays alone fail to identify all pathogenic variants. Kinase activity assays on purified variant proteins, clinical cohort analysis Genetics in medicine Medium 29925964
2018 The MYLK missense variant Ala1491Ser reduces kinase activity compared to wild-type protein and causes thoracic aortic aneurysm/dissection with a genotype-phenotype correlation: homozygous carriers have severe early-onset fatal disease while heterozygous carriers have mild late-onset disease. Kinase activity assay on recombinant variant protein, family clinical analysis Orphanet journal of rare diseases Medium 29544503
2019 A unique domain within MLCK1 (not present in other isoforms) directs its recruitment to the perijunctional actomyosin ring (PAMR); a small molecule 'divertin' blocks this domain-mediated MLCK1 recruitment without inhibiting enzymatic activity, thereby preventing TNF-induced MLC phosphorylation and barrier loss in vitro and in vivo. Domain deletion/mutagenesis, small molecule screen, live cell imaging, MLC phosphorylation assays, mouse barrier/diarrhea models, experimental IBD models Nature medicine High 30936544
2019 LPS increases intestinal epithelial tight junction permeability via TLR4/MyD88 activation of TAK-1, which activates NF-κB (p50/p65), leading to upregulation of MLCK (MYLK) expression and subsequent increased TJ permeability; siRNA silencing of TAK-1 or p65/p50 inhibited LPS-induced MLCK upregulation. siRNA knockdown of TAK-1, p65, p50, MLCK in Caco-2 cells and mouse models, TER/permeability assays The American journal of pathology Medium 30711488
2018 MYLK promotes hepatocellular carcinoma cell migration and invasion by phosphorylating myosin light chain (MLC), organizing F-actin stress fibers and cytoskeletal architecture, and facilitating epithelial-mesenchymal transition (increased Vimentin, N-cadherin, Snail; decreased E-cadherin). shRNA knockdown, wound-healing assay, Matrigel invasion, Western blot for phospho-MLC, F-actin staining Clinical and experimental medicine Medium 29855744
2022 SIK2 directly phosphorylates MYLK at Ser343, activating MYLK's downstream effector MYL2 (myosin light chain 2) phosphorylation, thereby promoting ovarian cancer cell motility and metastasis; adipocytes induce SIK2 phosphorylation at Ser358 and MYLK phosphorylation at Ser343 to enhance cancer cell motility. In vitro kinase assay, phospho-site identification, in vitro and in vivo migration/metastasis assays Molecular oncology Medium 35278271
2022 The m6A methyltransferase METTL3 promotes stability of MYLK mRNA through m6A modification, thereby promoting trophoblast cell invasion; MYLK overexpression rescues the impaired invasion caused by METTL3 depletion. m6A sequencing, shRNA knockdown, MYLK overexpression rescue, xCELLigence invasion assay Placenta Medium 36170767
2024 miR-1204 directly targets MYLK mRNA, reducing MYLK expression in vascular smooth muscle cells (VSMCs), leading to acquisition of a senescence-associated secretory phenotype (SASP) and loss of contractile phenotype; MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP, and contractile phenotypic changes and restores TGF-β signaling. miRNA target validation, MYLK overexpression rescue, mouse AAD models, angiotensin II and BAPN-induced models Nature communications Medium 39013850
2024 IGF2BP3 (m6A reader) binds MYLK mRNA in an m6A-dependent manner to extend its half-life and increase MYLK protein levels; elevated MYLK inhibits ERK1/2 phosphorylation, thereby repressing MSC adipogenesis. m6A-RIP, mRNA stability assay, siRNA/shRNA knockdown, ERK1/2 phosphorylation assay, adipogenesis assay, AAV overexpression in mice Cellular and molecular life sciences Medium 38196046
2018 In C. elegans, MLCK-1 (ortholog of MYLK) relocalizes from apical cell boundaries to basal actomyosin bundles during spermathecae contraction, stabilizing myosin downstream of calcium signaling; MLCK and ROCK act in distinct cell subsets to coordinate the timing of contraction. Live imaging, GFP-tagging, genetic analysis in C. elegans Molecular biology of the cell Medium 30088798

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Circular RNA MYLK as a competing endogenous RNA promotes bladder cancer progression through modulating VEGFA/VEGFR2 signaling pathway. Cancer letters 393 28687357
1992 X-ray structure determination of telokin, the C-terminal domain of myosin light chain kinase, at 2.8 A resolution. Journal of molecular biology 144 1404391
2019 Intracellular MLCK1 diversion reverses barrier loss to restore mucosal homeostasis. Nature medicine 143 30936544
2004 A differentiation-dependent splice variant of myosin light chain kinase, MLCK1, regulates epithelial tight junction permeability. The Journal of biological chemistry 141 15507455
1998 Acceleration of myosin light chain dephosphorylation and relaxation of smooth muscle by telokin. Synergism with cyclic nucleotide-activated kinase. The Journal of biological chemistry 117 9556631
1999 A single human myosin light chain kinase gene (MLCK; MYLK). Genomics 110 10198165
1991 The carboxyl terminus of the smooth muscle myosin light chain kinase is expressed as an independent protein, telokin. The Journal of biological chemistry 103 1748667
2020 LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 97 33168027
2005 KRP-203, a novel synthetic immunosuppressant, prolongs graft survival and attenuates chronic rejection in rat skin and heart allografts. Circulation 97 15642767
2019 Lipopolysaccharide-Induced Increase in Intestinal Permeability Is Mediated by TAK-1 Activation of IKK and MLCK/MYLK Gene. The American journal of pathology 84 30711488
2007 A novel sphingosine 1-phosphate receptor agonist, 2-amino-2-propanediol hydrochloride (KRP-203), regulates chronic colitis in interleukin-10 gene-deficient mice. The Journal of pharmacology and experimental therapeutics 81 17898319
2011 A transcribed pseudogene of MYLK promotes cell proliferation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 75 21441351
1996 Telokin expression is mediated by a smooth muscle cell-specific promoter. The American journal of physiology 74 8764148
2018 Circular RNA Myosin Light Chain Kinase (MYLK) Promotes Prostate Cancer Progression through Modulating Mir-29a Expression. Medical science monitor : international medical journal of experimental and clinical research 69 29798970
2017 Loss-of-Function Variants in MYLK Cause Recessive Megacystis Microcolon Intestinal Hypoperistalsis Syndrome. American journal of human genetics 60 28602422
2015 The ZEB1/miR-200c feedback loop regulates invasion via actin interacting proteins MYLK and TKS5. Oncotarget 60 26334100
2006 Regulation of myosin light chain kinase and telokin expression in smooth muscle tissues. American journal of physiology. Cell physiology 60 16774989
2006 Smooth muscle of telokin-deficient mice exhibits increased sensitivity to Ca2+ and decreased cGMP-induced relaxation. Proceedings of the National Academy of Sciences of the United States of America 57 16461919
2013 KRP-203, sphingosine 1-phosphate receptor type 1 agonist, ameliorates atherosclerosis in LDL-R-/- mice. Arteriosclerosis, thrombosis, and vascular biology 54 23640484
1994 Isolation and characterization of krp, a dibasic endopeptidase required for cell viability in the fission yeast Schizosaccharomyces pombe. The EMBO journal 54 7813430
2007 Effects of imidafenacin (KRP-197/ONO-8025), a new anti-cholinergic agent, on muscarinic acetylcholine receptors. High affinities for M3 and M1 receptor subtypes and selectivity for urinary bladder over salivary gland. Arzneimittel-Forschung 52 17396619
2018 Vibegron (RVT-901/MK-4618/KRP-114V) Administered Once Daily as Monotherapy or Concomitantly with Tolterodine in Patients with an Overactive Bladder: A Multicenter, Phase IIb, Randomized, Double-blind, Controlled Trial. European urology 50 30661513
1999 A genomic region encompassing a cluster of olfactory receptor genes and a myosin light chain kinase (MYLK) gene is duplicated on human chromosome regions 3q13-q21 and 3p13. Genomics 50 10036190
2007 Pharmacological effects of imidafenacin (KRP-197/ONO-8025), a new bladder selective anti-cholinergic agent, in rats. Comparison of effects on urinary bladder capacity and contraction, salivary secretion and performance in the Morris water maze task. Arzneimittel-Forschung 48 17469649
2018 MYLK pathogenic variants aortic disease presentation, pregnancy risk, and characterization of pathogenic missense variants. Genetics in medicine : official journal of the American College of Medical Genetics 46 29925964
2011 Analyses of phylogeny, evolution, conserved sequences and genome-wide expression of the ICK/KRP family of plant CDK inhibitors. Annals of botany 46 21385782
2006 Use of sphingosine-1-phosphate 1 receptor agonist, KRP-203, in combination with a subtherapeutic dose of cyclosporine A for rat renal transplantation. Transplantation 45 17006328
1997 Telokin expression in A10 smooth muscle cells requires serum response factor. The American journal of physiology 45 9142867
2001 Site-specific phosphorylation and point mutations of telokin modulate its Ca2+-desensitizing effect in smooth muscle. The Journal of biological chemistry 44 11346659
2020 Got Mylk? The Emerging Role of Australian Plant-Based Milk Alternatives as A Cow's Milk Substitute. Nutrients 41 32354190
1995 Immunolocalization of the heterotrimeric kinesin-related protein KRP(85/95) in the mitotic apparatus of sea urchin embryos. Developmental biology 41 7556895
2019 Circular RNA MYLK promotes hepatocellular carcinoma progression by increasing Rab23 expression by sponging miR-362-3p. Cancer cell international 40 31413665
2020 Circular RNA MYLK promotes tumour growth and metastasis via modulating miR-513a-5p/VEGFC signalling in renal cell carcinoma. Journal of cellular and molecular medicine 39 32342645
2006 130-kDa smooth muscle myosin light chain kinase is transcribed from a CArG-dependent, internal promoter within the mouse mylk gene. American journal of physiology. Cell physiology 39 16407417
2012 Hypermethylated FAM5C and MYLK in serum as diagnosis and pre-warning markers for gastric cancer. Disease markers 38 22377736
2022 SIK2 promotes ovarian cancer cell motility and metastasis by phosphorylating MYLK. Molecular oncology 35 35278271
2016 Myosin Light Chain Kinase MYLK1: Anatomy, Interactions, Functions, and Regulation. Biochemistry. Biokhimiia 35 28260490
2018 MYLK promotes hepatocellular carcinoma progression through regulating cytoskeleton to enhance epithelial-mesenchymal transition. Clinical and experimental medicine 34 29855744
2019 Circular RNA MYLK serves as an oncogene to promote cancer progression via microRNA-195/cyclin D1 axis in laryngeal squamous cell carcinoma. Bioscience reports 33 31427478
1998 A 310-bp minimal promoter mediates smooth muscle cell-specific expression of telokin. The American journal of physiology 33 9612204
2005 Telokin mediates Ca2+-desensitization through activation of myosin phosphatase in phasic and tonic smooth muscle. Journal of muscle research and cell motility 31 15750850
2000 Phosphorylation of telokin by cyclic nucleotide kinases and the identification of in vivo phosphorylation sites in smooth muscle. FEBS letters 30 10981712
2019 Silencing of long noncoding RNA SRRM2-AS exerts suppressive effects on angiogenesis in nasopharyngeal carcinoma via activating MYLK-mediated cGMP-PKG signaling pathway. Journal of cellular physiology 29 31742692
2024 Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice. Nature communications 27 39013850
2020 Circular RNA MYLK Promotes Glycolysis and Proliferation of Non-Small Cell Lung Cancer Cells by Sponging miR-195-5p and Increasing Glucose Transporter Member 3 Expression. Cancer management and research 26 32753964
2000 A kinesin-related protein, KRP(180), positions prometaphase spindle poles during early sea urchin embryonic cell division. The Journal of cell biology 26 10931863
1997 Telokin (kinase-related protein) modulates the oligomeric state of smooth-muscle myosin light-chain kinase and its interaction with myosin filaments. The Biochemical journal 26 9078244
2020 CircRNA_MYLK promotes malignant progression of ovarian cancer through regulating microRNA-652. European review for medical and pharmacological sciences 24 32495861
2016 A novel variant in MYLK causes thoracic aortic dissections: genotypic and phenotypic description. BMC medical genetics 24 27586135
2011 Bacteriophage P22 capsid size determination: roles for the coat protein telokin-like domain and the scaffolding protein amino-terminus. Virology 24 21784500
2021 LncRNA MYLK-AS1 acts as an oncogene by epigenetically silencing large tumor suppressor 2 (LATS2) in gastric cancer. Bioengineered 23 34181498
2019 New Cell-Penetrating Peptide (KRP) with Multiple Physicochemical Properties Endows Doxorubicin with Tumor Targeting and Improves Its Therapeutic Index. ACS applied materials & interfaces 23 30576099
2007 A novel sphingosine-1-phosphate receptor agonist KRP-203 attenuates rat autoimmune myocarditis. Biochemical and biophysical research communications 23 17673173
2001 Telokin expression is restricted to smooth muscle tissues during mouse development. American journal of physiology. Cell physiology 23 11121372
2018 Myosin light chain kinase ( MYLK) coding polymorphisms modulate human lung endothelial cell barrier responses via altered tyrosine phosphorylation, spatial localization, and lamellipodial protrusions. Pulmonary circulation 22 29480069
2017 Mechanical Stress and Single Nucleotide Variants Regulate Alternative Splicing of the MYLK Gene. American journal of respiratory cell and molecular biology 22 27529643
2019 Androgen receptor variant 12 promotes migration and invasion by regulating MYLK in gastric cancer. The Journal of pathology 21 30737779
2014 A MYLK variant regulates asthmatic inflammation via alterations in mRNA secondary structure. European journal of human genetics : EJHG 21 25271083
2018 Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype. Orphanet journal of rare diseases 20 29544503
2002 Translocation of telokin by cGMP signaling in smooth muscle cells. American journal of physiology. Cell physiology 19 12176732
2001 Phosphorylation of kinase-related protein (telokin) in tonic and phasic smooth muscles. Journal of muscle research and cell motility 19 11964068
1992 Molecular cloning of the chicken gizzard telokin gene and cDNA. Archives of biochemistry and biophysics 19 1444462
1992 Analytical sedimentation studies of turkey gizzard myosin light chain kinase and telokin. Biophysical journal 19 1617144
2011 An intronic MYLK variant associated with inflammatory lung disease regulates promoter activity of the smooth muscle myosin light chain kinase isoform. Journal of molecular medicine (Berlin, Germany) 18 22015949
2004 Activation of the smooth muscle-specific telokin gene by thyrotroph embryonic factor (TEF). The Journal of biological chemistry 18 14702338
2022 The m6A methyltransferase METTL3 promotes trophoblast cell invasion by regulating MYLK expression. Placenta 17 36170767
2020 Circular RNA MYLK Promotes Hepatocellular Carcinoma Progression Through the miR29a/KMT5C Signaling Pathway. OncoTargets and therapy 17 32904604
2018 The Splicing Factor hnRNPA1 Regulates Alternate Splicing of the MYLK Gene. American journal of respiratory cell and molecular biology 17 29077485
2012 Molecular mechanism of telokin-mediated disinhibition of myosin light chain phosphatase and cAMP/cGMP-induced relaxation of gastrointestinal smooth muscle. The Journal of biological chemistry 17 22544752
2007 Expression of kallikrein-related peptidases (KRP/hK5, 7, 6, 8) in subtypes of human lung carcinoma. International immunopharmacology 17 18182244
2020 circRNA MYLK Accelerates Cervical Cancer via Up-Regulation of RHEB and Activation of mTOR Signaling. Cancer management and research 16 32547198
2017 Exploiting cell cycle inhibitor genes of the KRP family to control root-knot nematode induced feeding sites in plants. Plant, cell & environment 16 28103637
2005 Modulation of myosin filament activation by telokin in smooth muscle liberation of myosin kinase and phosphatase from supramolecular complexes. Biophysical chemistry 15 15617808
2021 Silencing of long noncoding RNA MYLK-AS1 suppresses nephroblastoma via down-regulation of CCNE1 through transcription factor TCF7L2. Journal of cellular physiology 14 33438217
2020 Long noncoding RNA MYLK-AS1 promotes growth and invasion of hepatocellular carcinoma through the EGFR/HER2-ERK1/2 signaling pathway. International journal of biological sciences 14 32398965
2006 Efficacy of mycophenolic acid combined with KRP-203, a novel immunomodulator, in a rat heart transplantation model. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 14 16507424
2002 Smooth muscle myosin filament assembly under control of a kinase-related protein (KRP) and caldesmon. Journal of muscle research and cell motility 14 12630709
2024 IGF2BP3-mediated enhanced stability of MYLK represses MSC adipogenesis and alleviates obesity and insulin resistance in HFD mice. Cellular and molecular life sciences : CMLS 13 38196046
2018 The myosin light-chain kinase MLCK-1 relocalizes during Caenorhabditis elegans ovulation to promote actomyosin bundle assembly and drive contraction. Molecular biology of the cell 13 30088798
1997 Kinase-related protein (telokin) is phosphorylated by smooth-muscle myosin light-chain kinase and modulates the kinase activity. The Biochemical journal 13 9371697
2023 Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming. Antioxidants (Basel, Switzerland) 12 37891870
2017 Plant Cyclin-Dependent Kinase Inhibitors of the KRP Family: Potent Inhibitors of Root-Knot Nematode Feeding Sites in Plant Roots. Frontiers in plant science 12 28943880
2015 Structure-Function Analysis of the Non-Muscle Myosin Light Chain Kinase (nmMLCK) Isoform by NMR Spectroscopy and Molecular Modeling: Influence of MYLK Variants. PloS one 12 26111161
2011 In vivo efficacy of KRP-109, a novel elastase inhibitor, in a murine model of severe pneumococcal pneumonia. Pulmonary pharmacology & therapeutics 12 21864700
2006 Change from cyclosporine to combination therapy of mycophenolic acid with the new sphingosine-1-phosphate receptor agonist, KRP-203, prevents host nephrotoxicity and transplant vasculopathy in rats. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 12 16818126
1998 Regulation of the cross-bridge cycle: the effects of MgADP, LC17 isoforms and telokin. Acta physiologica Scandinavica 12 9887962
2021 miR-181a-2-3p Stimulates Gastric Cancer Progression via Targeting MYLK. Frontiers in bioengineering and biotechnology 11 34733825
2015 ROCK2 and MYLK variants under hypobaric hypoxic environment of high altitude associate with high altitude pulmonary edema and adaptation. The application of clinical genetics 11 26586960
2008 Telokin expression and the effect of hypoxia on its phosphorylation status in smooth muscle cells from small and large pulmonary arteries. American journal of physiology. Lung cellular and molecular physiology 11 18375742
1997 Characterization of the chicken telokin heterogeneity by time-of-flight mass spectrometry. Biochemistry 11 9283094
2023 GPR65 inhibits human trophoblast cell adhesion through upregulation of MYLK and downregulation of fibronectin via cAMP-ERK signaling in a low pH environment. Cell communication and signaling : CCS 10 37723567
2023 Chitosan-gentamicin conjugate attenuates heat stress-induced intestinal barrier injury via the TLR4/STAT6/MYLK signaling pathway: In vitro and in vivo studies. Carbohydrate polymers 10 37739521
2012 NMR assignments for the telokin-like domain of bacteriophage P22 coat protein. Biomolecular NMR assignments 10 22987227
2005 A novel immunomodulator KRP-203 combined with cyclosporine prolonged graft survival and abrogated transplant vasculopathy in rat heart allografts. Transplantation proceedings 10 15808575
2015 Deletion of Mylk1 in oocytes causes delayed morula-to-blastocyst transition and reduced fertility without affecting folliculogenesis and oocyte maturation in mice. Biology of reproduction 9 25761595
2025 MYLK-AS1 Enhances Glutamine Metabolism to Promote EGFR Inhibitor Resistance in Non-Small Cell Lung Cancer. Cancer research 8 40366631
2023 MYLK and CALD1 as molecular targets in bladder cancer. Medicine 8 38013282
2010 Genetic variation in MYLK and lung injury in children and adults with community-acquired pneumonia. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 8 20081554
2024 Activation of the ROCK/MYLK Pathway Affects Complex Molecular and Morphological Changes of the Trabecular Meshwork Associated With Ocular Hypertension. Investigative ophthalmology & visual science 7 39115865
1994 Sequence and expression of a baculovirus protein with antigenic similarity to telokin. The Journal of general virology 7 7517434

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