Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

MYLK (Myosin Light Chain Kinase)

  • Thomas J. Lukas
  • Vladimir P. Shirinsky
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_248

Synonyms

Historical Background

The gene for myosin light chain kinase encodes three proteins: MLCK210, MLCK108, and telokin/kinase-related protein (KRP). The first protein discovered was MLCK108 (Mr = 110–140 kDa) as a major cytoplasmic component of smooth muscle and responsible for smooth muscle contractility through the phosphorylation of the regulatory light chain of myosin (Lukas et al. 1998; Kamm and Stull 2001). MLCK210 (Mr = 210–220 kDa) has an amino-terminal extension containing additional protein-binding elements (Fig. 1). It was discovered ∼15 years later before the gene for MYLK was characterized from chicken (Birukov et al. 1998) and humans (Shen et al. 2012). Both MLCKs are Ca 2+-calmodulin-dependent enzymes. Telokin/KRP is an independently expressed nonkinase gene product containing the C-terminus of MLCK, and functions as a myosin-binding and...
This is a preview of subscription content, log in to check access.

References

  1. Adyshev DM, Moldobaeva N, Mapes B, Elangovan V, Garcia JG. MicroRNA regulation of nonmuscle myosin light chain kinase expression in human lung endothelium. Am J Respir Cell Mol Biol. 2013;49(1):58–66.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Al-Sadi R, Guo S, Ye D, Rawat M, Ma TY. TNF-alpha modulation of intestinal tight junction permeability is mediated by NIK/IKK-alpha axis activation of the canonical NF-kappaB pathway. Am J Pathol. 2016;186(5):1151–65.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Basu S, Proweller A. Autoregulatory control of smooth muscle myosin light chain kinase promoter by notch signaling. J Biol Chem. 2016;291(6):2988–99.CrossRefPubMedGoogle Scholar
  4. Birukov KG, Schavocky JP, Shirinsky VP, Chibalina MV, Van Eldik LJ, Watterson DM. Organization of the genetic locus for chicken myosin light chain kinase is complex: multiple proteins are encoded and exhibit differential expression and localization. J Cell Biochem. 1998;70(3):402–13.CrossRefPubMedGoogle Scholar
  5. Cunningham KE, Turner JR. Myosin light chain kinase: pulling the strings of epithelial tight junction function. Ann N Y Acad Sci. 2012;1258:34–42.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Dulyaninova NG, Bresnick AR. The long myosin light chain kinase is differentially phosphorylated during interphase and mitosis. Exp Cell Res. 2004;299(2):303–14.CrossRefPubMedGoogle Scholar
  7. Herring BP, El-Mounayri O, Gallagher PJ, Yin F, Zhou J. Regulation of myosin light chain kinase and telokin expression in smooth muscle tissues. Am J Physiol Cell Physiol. 2006;291(5):C817–27.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. PhosphoSitePlus, 2014: mutations, PTMs and Recalibrations. Nucleic Acids Res. 2015;43(Database issue):D512–20.CrossRefPubMedGoogle Scholar
  9. Kamm KE, Stull JT. Dedicated myosin light chain kinases with diverse cellular functions. J Biol Chem. 2001;276(7):4527–30.CrossRefPubMedGoogle Scholar
  10. Khapchaev AY, Shirinsky VP. Myosin light chain kinase MYLK1: Anatomy, interactions, functions, and regulation. Biochemistry (Moscow). 2016;81(13):1676–97. doi:10.1134/s000629791613006xCrossRefGoogle Scholar
  11. Khromov AS, Momotani K, Jin L, Artamonov MV, Shannon J, Eto M, et al. Molecular mechanism of telokin-mediated disinhibition of myosin light chain phosphatase and cAMP/cGMP-induced relaxation of gastrointestinal smooth muscle. J Biol Chem. 2012;287(25):20975–85.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Kudryashov DS, Stepanova OV, Vilitkevich EL, Nikonenko TA, Nadezhdina ES, Shanina NA, et al. Myosin light chain kinase (210 kDa) is a potential cytoskeleton integrator through its unique N-terminal domain. Exp Cell Res. 2004;298(2):407–17.CrossRefPubMedGoogle Scholar
  13. Lukas TJ, Mirzoeva S, Watterson DM. Calmodulin-regulated protein kinases. In: Van Eldik LJ, Watterson DM, editors. Calmodulin and signal transduction. New York: Academic; 1998. p. 66–168.Google Scholar
  14. Lukas TJ, Miao H, Chen L, Riordan SM, Li W, Crabb AM, et al. Susceptibility to glaucoma: differential comparison of the astrocyte transcriptome from glaucomatous African American and Caucasian American donors. Genome Biol. 2008;9(7):R111.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Shcherbakova OV, Serebryanaya DV, Postnikov AB, Schroeter MM, Zittrich S, Noegel AA, et al. Kinase-related protein/telokin inhibits Ca2+−independent contraction in Triton-skinned guinea pig taenia coli. Biochem J. 2010;429(2):291–302.CrossRefPubMedGoogle Scholar
  16. Shen K, Wang T, Garcia JG. MYLK (myosin light chain kinase). Atlas Genet Cytogenet Oncol Haematol. 2012;16(12):901–8.Google Scholar
  17. Shimizu Y, Camp SM, Sun X, Zhou T, Wang T, Garcia JG. Sp1-mediated nonmuscle myosin light chain kinase expression and enhanced activity in vascular endothelial growth factor-induced vascular permeability. Pulm Circ. 2015;5(4):707–15.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Shirinsky VP, Vorotnikov AV, Birukov KG, Nanaev AK, Collinge M, Lukas TJ, et al. A kinase-related protein stabilizes unphosphorylated smooth muscle myosin minifilaments in the presence of ATP. J Biol Chem. 1993;268(22):16578–83.PubMedGoogle Scholar
  19. Stephens NL, Cheng ZQ, Fust A. Sensitized airway smooth muscle plasticity and hyperreactivity: a review. Can J Physiol Pharmacol. 2007;85(7):679–85.CrossRefPubMedGoogle Scholar
  20. Takizawa N, Ikebe R, Ikebe M, Luna EJ. Supervillin slows cell spreading by facilitating myosin II activation at the cell periphery. J Cell Sci. 2007;120(Pt 21):3792–803.CrossRefPubMedGoogle Scholar
  21. Tan J, Wang Y, Xia Y, Zhang N, Sun X, Yu T, et al. Melatonin protects the esophageal epithelial barrier by suppressing the transcription, expression and activity of myosin light chain kinase through ERK1/2 signal transduction. Cell Physiol Biochem. 2014;34(6):2117–27.CrossRefPubMedGoogle Scholar
  22. Vilitkevich EL, Khapchaev AY, Kudryashov DS, Nikashin AV, Schavocky JP, Lukas TJ, et al. Phosphorylation regulates interaction of 210-kDa myosin light chain kinase N-terminal domain with actin cytoskeleton. Biochemistry (Mosc). 2015;80(10):1288–97.CrossRefGoogle Scholar
  23. Wadgaonkar R, Dudek SM, Zaiman AL, Linz-McGillem L, Verin AD, Nurmukhambetova S, et al. Intracellular interaction of myosin light chain kinase with macrophage migration inhibition factor (MIF) in endothelium. J Cell Biochem. 2005;95(4):849–58.CrossRefPubMedGoogle Scholar
  24. Weber M, Kim S, Patterson N, Rooney K, Searles CD. MiRNA-155 targets myosin light chain kinase and modulates actin cytoskeleton organization in endothelial cells. Am J Physiol Heart Circ Physiol. 2014;306(8):H1192–203.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Xu J, Gao XP, Ramchandran R, Zhao YY, Vogel SM, Malik AB. Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating beta2 integrins. Nat Immunol. 2008;9(8):880–6.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PharmacologyNorthwestern UniversityChicagoUSA
  2. 2.Institute of Experimental CardiologyRussian Cardiology Research and Production Complex, Ministry of Healthcare of Russian FederationMoscowRussia