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Gene Review

MYLK  -  myosin light chain kinase

Homo sapiens

Synonyms: AAT7, KRP, Kinase-related protein, MLCK, MLCK1, ...
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Disease relevance of MYLK

  • These data strongly implicate MYLK genetic variants to confer increased risk of sepsis and sepsis-associated ALI [1].
  • When added to contracting solution at the peak of a contracture, anti-MLCK Fab elicited a relaxation that was complete in about 120 minutes despite the presence of Ca2+ [2].
  • To localize the actin- and myosin-binding activities in the MLCK molecule and to examine their possible role in regulating the actin-myosin interaction, we expressed various fragments of cDNA encoding MLCK in Escherichia coli as recombinant proteins [3].
  • Genetic variants in MYLK are significantly associated with both asthma and sepsis in populations of African ancestry [4].

High impact information on MYLK

  • Ca2+ sensitivity of smooth muscle and nonmuscle myosin II reflects the ratio of activities of myosin light-chain kinase (MLCK) to myosin light-chain phosphatase (MLCP) and is a major, regulated determinant of numerous cellular processes [5].
  • These data indicate that MLCK is a target for PAKs and that PAKs may regulate cytoskeletal dynamics by decreasing MLCK activity and MLC phosphorylation [6].
  • MLCK activity and MLC phosphorylation were decreased, and cell spreading was inhibited in baby hamster kidney-21 and HeLa cells expressing constitutively active PAK1 [6].
  • F-actin was decorated with a peptide containing the NH2-terminal 147 residues of MLCK (MLCK-147) that binds to F-actin with high affinity [7].
  • It is widely accepted that actin filaments and the conventional double-headed myosin interact to generate force for many types of nonmuscle cell motility, and that this interaction occurs when the myosin regulatory light chain (MLC) is phosphorylated by MLC kinase (MLCK) together with calmodulin and Ca(2+) [8].

Biological context of MYLK


Anatomical context of MYLK

  • Phosphorylation of myosin II regulatory light chains (RLC) by Ca(2+)/calmodulin-dependent myosin light chain kinase (MLCK) is a critical step in the initiation of smooth muscle and non-muscle cell contraction [11].
  • In interphase cells, localization of the long MLCK to stress fibers is mediated by five DXRXXL motifs, which span the junction of the NH(2)-terminal extension and the short MLCK [12].
  • These data suggest that the novel 214-kD kinase, the only MLCK isoform found in endothelium, may be preferentially expressed in this nonmuscle tissue [13].
  • The phosphorylation of myosin light chains by myosin light chain kinase (MLCK) is a key event in agonist-mediated endothelial cell gap formation and vascular permeability [14].
  • Monitoring of MLCK expression in different cell types with antibodies generated against a unique human EC MLCK N-terminal sequence revealed a high level of expression of the 214-kD enzyme in endothelium, minimal level of expression in smooth muscle, and no expression in skeletal muscle [13].

Associations of MYLK with chemical compounds


Regulatory relationships of MYLK


Other interactions of MYLK

  • Cdc42-activated placenta and recombinant, constitutively active PAK2 phosphorylate MLCK in vitro with a stoichiometry of 1.71 +/- 0 [11].
  • Previous studies from our laboratory suggested that the TNF-alpha-induced increase in intestinal TJ permeability was mediated by an increase in myosin light chain kinase (MLCK) protein expression [20].
  • Phosphorylation of myosin regulatory light chain may be mediated directly and indirectly by several kinases including myosin light chain kinase (MLCK) and kinases activated by small GTP-binding proteins [21].

Analytical, diagnostic and therapeutic context of MYLK

  • Furthermore, compared with platelets and cells expressing the Leu(33) isoform, the Pro(33) variant showed greater alpha-granule release, clot retraction, and adhesion to fibrinogen under shear stress, and these functional differences were abolished by MLCK and MAPK kinase inhibition [15].
  • Immunofluorescence studies reveal rapid, Rac-dependent translocation of cortactin to the expanded cortical actin band following S1P challenge, where colocalization with EC MLCK occurs within 5 min [22].
  • Sequence analysis also identified, however, a 5' stretch of novel sequence (amino acids #1-922) which is not contained in the open reading frame of mammalian SM MLCK, and is only 58% homologous to the avian fibroblast MLCK sequence [14].
  • The chromosomal localization of the gene for human MLCK is shown to be at 3qcen-q21, as determined by PCR and Southern blotting using two somatic cell hybrid panels [23].
  • We examined MLCK activation quantitatively with a fluorescent biosensor MLCK where Ca(2+)-dependent increases in kinase activity were coincident with decreases in fluorescence resonance energy transfer (FRET) in vitro [24].


  1. Novel polymorphisms in the myosin light chain kinase gene confer risk for acute lung injury. Gao, L., Grant, A., Halder, I., Brower, R., Sevransky, J., Maloney, J.P., Moss, M., Shanholtz, C., Yates, C.R., Meduri, G.U., Shriver, M.D., Ingersoll, R., Scott, A.F., Beaty, T.H., Moitra, J., Ma, S.F., Ye, S.Q., Barnes, K.C., Garcia, J.G. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  2. Effects of antibodies to myosin light chain kinase on contractility and myosin phosphorylation in chemically permeabilized smooth muscle. De Lanerolle, P., Strauss, J.D., Felsen, R., Doerman, G.E., Paul, R.J. Circ. Res. (1991) [Pubmed]
  3. Structure and function of smooth muscle myosin light chain kinase. Kishi, H., Ye, L.H., Nakamura, A., Okagaki, T., Iwata, A., Tanaka, T., Kohama, K. Adv. Exp. Med. Biol. (1998) [Pubmed]
  4. Polymorphisms in the myosin light chain kinase gene that confer risk of severe sepsis are associated with a lower risk of asthma. Gao, L., Grant, A.V., Rafaels, N., Stockton-Porter, M., Watkins, T., Gao, P., Chi, P., Muñoz, M., Watson, H., Dunston, G., Togias, A., Hansel, N., Sevransky, J., Maloney, J.P., Moss, M., Shanholtz, C., Brower, R., Garcia, J.G., Grigoryev, D.N., Cheadle, C., Beaty, T.H., Mathias, R.A., Barnes, K.C. J. Allergy Clin. Immunol. (2007) [Pubmed]
  5. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Somlyo, A.P., Somlyo, A.V. Physiol. Rev. (2003) [Pubmed]
  6. Inhibition of myosin light chain kinase by p21-activated kinase. Sanders, L.C., Matsumura, F., Bokoch, G.M., de Lanerolle, P. Science (1999) [Pubmed]
  7. Myosin light chain kinase binding to a unique site on F-actin revealed by three-dimensional image reconstruction. Hatch, V., Zhi, G., Smith, L., Stull, J.T., Craig, R., Lehman, W. J. Cell Biol. (2001) [Pubmed]
  8. Rho-kinase--mediated contraction of isolated stress fibers. Katoh, K., Kano, Y., Amano, M., Onishi, H., Kaibuchi, K., Fujiwara, K. J. Cell Biol. (2001) [Pubmed]
  9. 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. Brand-Arpon, V., Rouquier, S., Massa, H., de Jong, P.J., Ferraz, C., Ioannou, P.A., Demaille, J.G., Trask, B.J., Giorgi, D. Genomics (1999) [Pubmed]
  10. The functional myosin light chain kinase (MYLK) gene localizes with marker D3S3552 on human chromosome 3q21 in a >5-Mb yeast artificial chromosome region and is not linked to olfactory receptor genes. Giorgi, D., Brand-Arpon, V., Rouquier, S. Cytogenet. Cell Genet. (2001) [Pubmed]
  11. Phosphorylation of myosin light chain kinase by p21-activated kinase PAK2. Goeckeler, Z.M., Masaracchia, R.A., Zeng, Q., Chew, T.L., Gallagher, P., Wysolmerski, R.B. J. Biol. Chem. (2000) [Pubmed]
  12. Localization and activity of myosin light chain kinase isoforms during the cell cycle. Poperechnaya, A., Varlamova, O., Lin, P.J., Stull, J.T., Bresnick, A.R. J. Cell Biol. (2000) [Pubmed]
  13. Expression of a novel high molecular-weight myosin light chain kinase in endothelium. Verin, A.D., Lazar, V., Torry, R.J., Labarrere, C.A., Patterson, C.E., Garcia, J.G. Am. J. Respir. Cell Mol. Biol. (1998) [Pubmed]
  14. Myosin light chain kinase in endothelium: molecular cloning and regulation. Garcia, J.G., Lazar, V., Gilbert-McClain, L.I., Gallagher, P.J., Verin, A.D. Am. J. Respir. Cell Mol. Biol. (1997) [Pubmed]
  15. Enhanced activation of mitogen-activated protein kinase and myosin light chain kinase by the Pro33 polymorphism of integrin beta 3. Vijayan, K.V., Liu, Y., Dong, J.F., Bray, P.F. J. Biol. Chem. (2003) [Pubmed]
  16. Contractility as a Prerequisite for TGF-{beta}-Induced Myofibroblast Transdifferentiation in Human Tenon Fibroblasts. Meyer-Ter-Vehn, T., Sieprath, S., Katzenberger, B., Gebhardt, S., Grehn, F., Schlunck, G. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  17. Analysis of the kinase-related protein gene found at human chromosome 3q21 in a multi-gene cluster: organization, expression, alternative splicing, and polymorphic marker. Watterson, D.M., Schavocky, J.P., Guo, L., Weiss, C., Chlenski, A., Shirinsky, V.P., Van Eldik, L.J., Haiech, J. J. Cell. Biochem. (1999) [Pubmed]
  18. EPEC-activated ERK1/2 participate in inflammatory response but not tight junction barrier disruption. Savkovic, S.D., Ramaswamy, A., Koutsouris, A., Hecht, G. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  19. Cellular and molecular mechanisms that mediate basal and tumour necrosis factor-alpha-induced regulation of myosin light chain kinase gene activity. Ye, D., Ma, T.Y. J. Cell. Mol. Med. (2008) [Pubmed]
  20. Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier. Ye, D., Ma, I., Ma, T.Y. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  21. Activation of myosin in HeLa cells causes redistribution of focal adhesions and F-actin from cell center to cell periphery. Szczepanowska, J., Korn, E.D., Brzeska, H. Cell Motil. Cytoskeleton (2006) [Pubmed]
  22. Pulmonary endothelial cell barrier enhancement by sphingosine 1-phosphate: roles for cortactin and myosin light chain kinase. Dudek, S.M., Jacobson, J.R., Chiang, E.T., Birukov, K.G., Wang, P., Zhan, X., Garcia, J.G. J. Biol. Chem. (2004) [Pubmed]
  23. The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing, expression, and localization to 3qcen-q21. Potier, M.C., Chelot, E., Pekarsky, Y., Gardiner, K., Rossier, J., Turnell, W.G. Genomics (1995) [Pubmed]
  24. Quantitative measurements of Ca(2+)/calmodulin binding and activation of myosin light chain kinase in cells. Geguchadze, R., Zhi, G., Lau, K.S., Isotani, E., Persechini, A., Kamm, K.E., Stull, J.T. FEBS Lett. (2004) [Pubmed]
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