MYLK2 explained

Myosin light chain kinase 2 also known as MYLK2 is an enzyme which in humans is encoded by the MYLK2 gene.^[1]

Function

This gene encodes a myosin light chain kinase, a calcium / calmodulin dependent enzyme, that is exclusively expressed in adult skeletal muscle.^[2] The MYLK2 gene expresses skMLCK more prevalently in fast twitch muscle fibers as compared to slow twitch muscle fibers. Calmodulin is composed of two terminal domains (N,C) each containing two E-F hand motifs that bind to Ca2+. Upon saturation of Ca2+, Calmodulin undergoes a conformation change allowing it to bind with a target protein such as skMLCK. An image depicting a similar complex (sdCen/skMLCK2) is shown under myosin light chain kinase. This binding to skMLCK increases the affinity of Ca2+ and ultimately leads to a sustained muscle action.^[3]

Clinical significance

Mutations in the MYLK2 gene have been linked to midventricular hypertrophic cardiomyopathy.^[1]

Further reading

• Jeronimo C, Forget D, Bouchard A . Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. . Mol. Cell . 27 . 2 . 262–74 . 2007 . 17643375 . 10.1016/j.molcel.2007.06.027 . 4498903.
• Junker JP, Rief M . Single-molecule force spectroscopy distinguishes target binding modes of calmodulin. . Proc. Natl. Acad. Sci. U.S.A. . 106 . 34 . 14361–6 . 2009 . 19667195 . 10.1073/pnas.0904654106 . 2732892 . 2009PNAS..10614361J . free .
• Roush CL, Kennelly PJ, Glaccum MB . Isolation of the cDNA encoding rat skeletal muscle myosin light chain kinase. Sequence and tissue distribution. . J. Biol. Chem. . 263 . 21 . 10510–6 . 1988 . 10.1016/S0021-9258(19)81545-4 . 2839493 . free .
• Christie JD, Ma SF, Aplenc R . Variation in the myosin light chain kinase gene is associated with development of acute lung injury after major trauma. . Crit. Care Med. . 36 . 10 . 2794–800 . 2008 . 18828194 . 10.1097/CCM.0b013e318186b843 . 6567908 .
• Lazar V, Garcia JG . A single human myosin light chain kinase gene (MLCK; MYLK). . Genomics . 57 . 2 . 256–67 . 1999 . 10198165 . 10.1006/geno.1999.5774 . free .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Deloukas P, Matthews LH, Ashurst J . The DNA sequence and comparative analysis of human chromosome 20. . Nature . 414 . 6866 . 865–71 . 2001. 11780052 . 10.1038/414865a . 2001Natur.414..865D . free . }
• Soung YH, Lee JW, Kim SY . Mutational analysis of the kinase domain of MYLK2 gene in common human cancers. . Pathol. Res. Pract. . 202 . 3 . 137–40 . 2006 . 16448786 . 10.1016/j.prp.2005.12.003 .
• Gallagher PJ, Herring BP, Stull JT . Myosin light chain kinases. . J. Muscle Res. Cell. Motil. . 18 . 1 . 1–16 . 1997 . 9147985 . 10.1023/A:1018616814417 . 11975486 .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Lanfranchi G, Muraro T, Caldara F. Identification of 4370 expressed sequence tags from a 3'-end-specific cDNA library of human skeletal muscle by DNA sequencing and filter hybridization. . Genome Res. . 6 . 1 . 35–42 . 1996 . 8681137 . 10.1101/gr.6.1.35 . free .
• Toth-Zsamboki E, Oury C, Cornelissen H . P2X1-mediated ERK2 activation amplifies the collagen-induced platelet secretion by enhancing myosin light chain kinase activation. . J. Biol. Chem. . 278 . 47 . 46661–7 . 2003 . 14500714 . 10.1074/jbc.M308452200 . free .

Notes and References

1. Davis JS, Hassanzadeh S, Winitsky S, Lin H, Satorius C, Vemuri R, Aletras AH, Wen H, Epstein ND . The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation . Cell . 107 . 5 . 631–41 . November 2001 . 11733062 . 10.1016/S0092-8674(01)00586-4 . 778253 . free .
2. Web site: Entrez Gene: MYLK2 myosin light chain kinase 2, skeletal muscle .
3. Stull JT, Kamm KE, Vandenboom R . Myosin light chain kinase and the role of myosin light chain phosphorylation in skeletal muscle . Arch Biochem Biophys . 510. 2. 120–8. February 2011 . 21284933 . 10.1016/j.abb.2011.01.017 . 3101293.