| Function |
Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis.
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| Gene References into Functions |
- miR155 directly suppressed the expression of MYLK without affecting the RhoA pathway. PMID: 29901087
- the MAPKspecific inhibitor SB203580 attenuated the inhibitory effects of 4HPR on the migration of HepG2 cells. Moreover, we also observed that 4HPR inhibited the activation and expression of myosin light chain kinase (MLCK) in HepG2 cells. PMID: 29767236
- Recombinant human MLCK was concentration- and time-dependently degraded by recombinant human MMP9 in vitro, and this process was prevented by the MMP9 inhibitor. PMID: 29262413
- High expression of MLCK is correlated with metastatic triple negative breast cancer. PMID: 27563827
- Interaction between kinase domain and regulatory light chain (RLC) substrate is identified in the absence of calmodulin, indicating restored substrate-binding capability due to mechanically induced removal of the auto-inhibitory regulatory region. PMID: 28696205
- loss of MLCK contributes to the migratory properties of epithelial cells resulting from changes in cell-cell and cell-matrix adhesions, and increased epidermal growth factor receptor signaling. PMID: 26876209
- Its phosphorylation and dephosphorylation regulate smooth muscle contraction and relaxation. PMID: 27375035
- Sixty-seven experienced runners competed in a marathon race. The MLCK genotype (C37885A) of these marathoners was determined. CA heterozygotes for MLCK C37885A might present higher exercise-induced muscle damage after a marathon competition than CC counterparts. PMID: 27483374
- three Megacystis microcolon intestinal hypoperistalsis syndrome (MMHS)-affected subjects from two consanguineous families with no variants in the known MMIHS-associated genes. PMID: 28602422
- these Acute respiratory distress syndrome (ARDS)-associated MYLK cytosine-guanine dinucleotides with effect modification by ethnicity and local modified cytosine quantitative trait loci suggest that MYLK epigenetic variation and local genetic background may contribute to health disparities observed in ARDS. PMID: 27543902
- mechanical stress and MYLK single nucleotide polymorphism regulate MYLK alternative splicing. PMID: 27529643
- Rebeccamycin attenuates TNF-alpha-induced disruption of intestinal epithelial barrier integrity by inducing claudin-5 expression and suppressing MLCK production via Chk1 activation. PMID: 28391269
- Data show that alterations in myosin light chain kinase activity, claudin-15 and claudin-2 expression are associated with gluten-induced symptomatology and intestinal permeability changes in diarrhea-predominant irritable bowel syndrome (IBS-D). PMID: 27869798
- PXR regulates the intestinal epithelial barrier during inflammation by modulating cytokine-induced MLCK expression and JNK1/2 activation PMID: 27440420
- A 2-bp deletion in myosin light chain kinase (c3272_3273del, p.Ser1091*) that led to a premature stop codon have a high risk of presenting with an acute aortic dissection or rupture. PMID: 27586135
- In contrast to mylk2 and mylk3, mylk1 has a complex structure, and multiple protein products of the mylk1 gene are expressed in most if not all cell types. This review deals with the mylk1 gene and its protein products- multiple MLCK isoforms and noncatalytic KRP/telokin protein. [Review] PMID: 28260490
- Likely pathogenic variants included a TGFB2 variant in one patient and a SMAD3 variant in another. These variants have been reported previously in individuals with similar phenotypes. Variants of uncertain significance of particular interest included novel variants in MYLK and MFAP5, which were identified in a third patient PMID: 26854089
- suggest a novel role for myosin light chain and myosin light chain kinase in advanced glycation end product-induced endothelial hyperpermeability PMID: 26607798
- TKS5 and MYLK represent two mediators of invasive behavior of cancer cells that are regulated by the ZEB1/miR-200 feedback loop PMID: 26334100
- We speculate that the drop of the ROCK-to-MLCK ratio may occur as an attempt to compensate for the increased Rho kinase activity. PMID: 26468005
- study demonstrates that G. duodenalis-mediated disruption of villin is, at least, in part dependent on activation of myosin light chain kinase (MLCK). PMID: 26334299
- Gene-based association analyses shows nominal significant association with multifocal fibromuscular dysplasia for myosin light chain kinase. PMID: 26147384
- These structure-function studies suggest novel mechanisms for nmMLCK regulation, which may confirm MYLK as a candidate gene in inflammatory lung disease and advance knowledge of the genetic underpinning of lung-related health disparities. PMID: 26111161
- nmMLCK variant (721C) mRNA secondary structure exhibits increased stability and greater efficiency in protein translation initiation. PMID: 25271083
- inhibition of p38 MAP kinase attenuated the histamine response in all three EC types. Inhibition of RhoA, ROCK, or MLCK also prevented the histamine-induced decrease in TER in HDMEC. PMID: 25582918
- Fine mapping of the myosin light chain kinase (MYLK) gene replicates the association with asthma in populations of Spanish descent. PMID: 26025125
- serum MLCK is associated with Type 2 diabetes mellitus. PMID: 25696011
- Data suggest that expression of MLCK, myosin light chain, and myosin heavy chain 11 (MYH11) is up-regulated in uterine myoma as compared to adjacent smooth muscle cells; phosphorylation/activation of MLCK appears to be involved in cell proliferation. PMID: 25181625
- The Smooth muscle myosin light chain kinase (MLCK) contributes to Ca(2+) flux regulation in vascular smooth muscle (VSM) and in non-muscle cells, where cytoskeleton has been suggested to help Ca(2+) channels trafficking. PMID: 25483583
- Melatonin protects the esophageal epithelial barrier by suppressing the transcription, translation and activity of MLCK through ERK1/2 signal transduction PMID: 25562159
- epithelial MLCK-activated brush border fanning by IFN-gamma promotes adherence and internalization of normally noninvasive enteric bacteria PMID: 24911373
- These findings suggested that low MYLK and MYL9 expressions might be associated with the development of NSCLC. PMID: 25179839
- IgE has a role in regulating smMLCK in HASM cells PMID: 24722483
- Increased human lung endothelial cell expression of MYLK by bioactive agonists (excessive mechanical stress, TNF-alpha) is regulated in part by specific miRNAs (miR-374a, miR-374b, miR-520c-3p, and miR-1290). PMID: 23492194
- Claudin-2 assumes an important role in colorectal inflammation, and furthermore implicates the involvement of MLCK in colon inflammation. PMID: 23306855
- these studies show that the IL-1beta-induced increase in intestinal tight junction permeability was regulated by p38 kinase activation of ATF-2 and by ATF-2 regulation of MLCK gene activity PMID: 23656735
- The approximate time period of changes in the ratios of MLCK-108 and MLCK-210 was revealed (between 8-9 and 13 weeks), that can be associated with functional changes in the developing myocardium. PMID: 22808459
- MYLK SNPs downregulate smooth muscle MLCK promoter activity due to interruption of a FOXN1 binding site. These data provide new insights into the contribution of MYLK SNPs to inflammatory disease susceptibility. PMID: 22015949
- MLCK is essential for the translocation and association of cortactin and p47phox. PMID: 22219181
- Hypermethylated FAM5C and MYLK in serum are strongly associated with the development of gastric cancer and can be used as potential biomarkers for diagnosis and pre-warning. PMID: 22377736
- IL-18 may potentiate inflammation in the context of inflammatory bowel disease by facilitating neutrophil transepithelial migration via MLCK-dependent disruption of tight junctional occludin. PMID: 22135309
- Results provide evidence that neutrophil transmigration is regulated by myosin light chain kinase-mediated endothelial cell contraction and that this event depends on subendothelial cell matrix stiffness. PMID: 21652678
- MLCK inhibits the restoration of GPIbalpha in PAR1 pathway during the course of thrombin receptor activation in platelets. PMID: 19549383
- No association between snps in the myosin light chain kinase gene and either the need for positive-pressure ventilation or the development of acute lung injury/acute respiratory distress syndrome was observed in children with community-acquired pneumonia. PMID: 20081554
- Studies indicate an essential role for Abl kinase in vascular barrier regulation via posttranslational modification of nmMLCK. PMID: 20861316
- genetic and functional studies support the conclusion that heterozygous loss-of-function mutations in MYLK are associated with aortic dissections. PMID: 21055718
- Data provide insights into the molecular basis for vascular barrier-regulatory cytoskeletal responses and quantified the critical interactions between non-muscle MLCK isoenzymes and cortactin during vascular barrier regulation. PMID: 20053363
- study concludes MLCK is responsible for high proliferative ability of breast cancer cells through anti-apoptosis, in which p38 pathway was involved PMID: 20453870
- membrane blebbing in response to AT(1)R signaling is dependent on beta-arrestin2 and is mediated by a RhoA/ROCK/MLCK-dependent pathway PMID: 20181817
- hARD1 is a bona fide regulator of MLCK, and hARD1 plays a crucial role in the balance between tumor cell migration and stasis PMID: 19826488
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| Involvement in disease |
Aortic aneurysm, familial thoracic 7 (AAT7) |
| Subcellular Location |
Cytoplasm. Cell projection, lamellipodium. Cleavage furrow. Cytoplasm, cytoskeleton, stress fiber. |
| Protein Families |
Protein kinase superfamily, CAMK Ser/Thr protein kinase family |
| Tissue Specificity |
Smooth muscle and non-muscle isozymes are expressed in a wide variety of adult and fetal tissues and in cultured endothelium with qualitative expression appearing to be neither tissue- nor development-specific. Non-muscle isoform 2 is the dominant splice |
| Database Links |
HGNC: 7590 OMIM: 600922 KEGG: hsa:4638 STRING: 9606.ENSP00000353452 UniGene: Hs.477375 |
