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Gene Review

MYLK2  -  myosin light chain kinase 2

Homo sapiens

Synonyms: KMLC, MLCK, MLCK2, Myosin light chain kinase 2, skeletal/cardiac muscle, skMLCK
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Disease relevance of MYLK2


High impact information on MYLK2

  • To test this hypothesis directly, we microinjected individual smooth muscle cells with modulators of the MLCK pathway while measuring contraction and calcium-ion concentration [4].
  • Despite only 30% identity in amino acid sequence, the MLCK sequence can be readily accommodated in this structure [5].
  • The active site of the modeled MLCK complements the known requirements for peptide substrate recognition [5].
  • RESULTS: PIK inhibited MLC kinase in vitro and was able to cross cell membranes and concentrate at the perijunctional actomyosin ring [3].
  • 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+) [6].

Biological context of MYLK2

  • Phosphorylation was inhibited by the calmodulin (CaM) inhibitor W-7, but not by the Rho kinase inhibitor HA-1077, i.e. it is exclusively regulated by Ca2+/CaM-dependent MLC kinase [7].
  • We analyzed exons 6 and 7 eccoding the kinase domain of MYLK2 for somatic mutations in 60 gastric, 104 colorectal, 79 non-small cell lung, and 54 breast cancers using a polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) [1].
  • The MYLK2 mutation detected was a missense mutation that would substitute an amino acid (E374D) However, there was no somatic mutation of the MYLK2 gene [1].
  • The total length of the rat skeletal muscle MLCK cDNA was 2823 base pairs with an open reading frame of 1830 base pairs [8].
  • Occupancy of both sites in the MLCK enzymes by TRCI results in only low levels of enzyme activation; occupancy of both sites by TRCII also results in low levels of gMLCK activity, but activates skMLCK activity to 65% of the maximum level [9].

Anatomical context of MYLK2

  • Myosin light chain kinase 2, skeletal muscle (MYLK2) encodes a calcium/calmodulin-dependent serine/threonine kinase [1].
  • We have investigated the abilities of calmodulin (CaM) tryptic fragments 1-75 (TRCI) or 78-148 (TRCII) to activate gizzard smooth muscle myosin light chain kinase (gMLCK), rabbit skeletal muscle myosin light chain kinase (skMLCK), and neural nitric oxide synthase (nNOS) activities [9].
  • Our results suggest that the ERK pathway regulates PE cell migration by affecting the formation of focal adhesions and lamellipodia through the action of myosin light chain kinase (MLCK) [10].
  • Early captopril treatment in SHR significantly inhibited Ras and MLCK expression at all ages and decreased ERK-P and MLC-P at 12 and 18 weeks in mesenteric arteries [11].
  • Potential MLCK-independent mechanisms of endothelial cell permeability were examined with little evidence to support a role for stimulated nitric oxide synthase or phospholipase A2 activities [12].

Associations of MYLK2 with chemical compounds

  • Correspondingly, the P2X1-induced platelet shape change was inhibited by W-7 and by the MLC kinase inhibitor ML-7 but not by HA-1077 [7].
  • We therefore conclude that at low doses of collagen, glycoprotein VI activation leads to early protein kinase C- and MLC kinase-dependent degranulation [7].
  • After exposure of the cells to ATL-1, myosin L chain kinase (MLCK) phosphorylation was evident and this effect was inhibited by PD98059 or Y-27632, a specific inhibitor of Rho kinase [13].
  • The sites of tyrosine phosphorylation catalyzed by p60(Src) are Tyr(464) and Tyr(471) within the 69-residue stretch deleted in the MLCK-2 splice variant [14].
  • The histamine-induced MLC phosphorylation was reduced by pre-exposure to either ML-7 (50 microM), an MLCK (MLC kinase) inhibitor, or chelerythrine (10 microM), an inhibitor of PKC [15].

Analytical, diagnostic and therapeutic context of MYLK2

  • Peptide mapping of MLC indicated phosphorylation by MLCK [16].
  • 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 [17].
  • RT-PCR using primer pairs that were designed to detect specifically nonmuscle MLCK isoforms 2, 3, and 4 deletions (D2, D3, and D4) confirmed expression in both human adult and human fetal tissues (lung, liver, brain, and kidney) and in human endothelial cells (umbilical vein and dermal) [18].
  • Northern blot analysis demonstrated the extended expression pattern of the nonmuscle MLCK isoform(s) in both human adult and human fetal tissues [18].
  • We strengthened this result by ex vivo experiments and evidenced an MLCK-dependent window in late G1 phase of regenerating liver after two-thirds partial hepatectomy [19].


  1. Mutational analysis of the kinase domain of MYLK2 gene in common human cancers. Soung, Y.H., Lee, J.W., Kim, S.Y., Nam, S.W., Park, W.S., Lee, J.Y., Yoo, N.J., Lee, S.H. Pathol. Res. Pract. (2006) [Pubmed]
  2. Absence of the mutation of serine/threonine kinase genes AKT2 and MYLK2 in acute leukemias. Soung, Y.H., Lee, J.W., Kim, S.Y., Nam, S.W., Kim, S.H., Lee, J.Y., Yoo, N.J., Lee, S.H. Eur. J. Haematol. (2006) [Pubmed]
  3. A membrane-permeant peptide that inhibits MLC kinase restores barrier function in in vitro models of intestinal disease. Zolotarevsky, Y., Hecht, G., Koutsouris, A., Gonzalez, D.E., Quan, C., Tom, J., Mrsny, R.J., Turner, J.R. Gastroenterology (2002) [Pubmed]
  4. Effects of modulators of myosin light-chain kinase activity in single smooth muscle cells. Itoh, T., Ikebe, M., Kargacin, G.J., Hartshorne, D.J., Kemp, B.E., Fay, F.S. Nature (1989) [Pubmed]
  5. Structural basis of the intrasteric regulation of myosin light chain kinases. Knighton, D.R., Pearson, R.B., Sowadski, J.M., Means, A.R., Ten Eyck, L.F., Taylor, S.S., Kemp, B.E. Science (1992) [Pubmed]
  6. 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]
  7. P2X1-mediated ERK2 activation amplifies the collagen-induced platelet secretion by enhancing myosin light chain kinase activation. Toth-Zsamboki, E., Oury, C., Cornelissen, H., De Vos, R., Vermylen, J., Hoylaerts, M.F. J. Biol. Chem. (2003) [Pubmed]
  8. Isolation of the cDNA encoding rat skeletal muscle myosin light chain kinase. Sequence and tissue distribution. Roush, C.L., Kennelly, P.J., Glaccum, M.B., Helfman, D.M., Scott, J.D., Krebs, E.G. J. Biol. Chem. (1988) [Pubmed]
  9. Activation of myosin light chain kinase and nitric oxide synthase activities by calmodulin fragments. Persechini, A., McMillan, K., Leakey, P. J. Biol. Chem. (1994) [Pubmed]
  10. Migration of F9 parietal endoderm cells is regulated by the ERK pathway. Hong, T., Grabel, L.B. J. Cell. Biochem. (2006) [Pubmed]
  11. Involvement of ras-regulated Myosin light chain phosphorylation in the captopril effects in spontaneously hypertensive rats. Hu, W.Y., Han, Y.J., Gu, L.Z., Piano, M., de Lanerolle, P. Am. J. Hypertens. (2007) [Pubmed]
  12. Mechanisms of ionomycin-induced endothelial cell barrier dysfunction. Garcia, J.G., Schaphorst, K.L., Shi, S., Verin, A.D., Hart, C.M., Callahan, K.S., Patterson, C.E. Am. J. Physiol. (1997) [Pubmed]
  13. Involvement of the Rho-kinase/myosin light chain kinase pathway on human monocyte chemotaxis induced by ATL-1, an aspirin-triggered lipoxin A4 synthetic analog. Simões, R.L., Fierro, I.M. J. Immunol. (2005) [Pubmed]
  14. Differential regulation of alternatively spliced endothelial cell myosin light chain kinase isoforms by p60(Src). Birukov, K.G., Csortos, C., Marzilli, L., Dudek, S., Ma, S.F., Bresnick, A.R., Verin, A.D., Cotter, R.J., Garcia, J.G. J. Biol. Chem. (2001) [Pubmed]
  15. Histamine-induced phosphorylation of the regulatory light chain of myosin II disrupts the barrier integrity of corneal endothelial cells. Srinivas, S.P., Satpathy, M., Guo, Y., Anandan, V. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  16. Volume-sensitive myosin phosphorylation in vascular endothelial cells: correlation with Na-K-2Cl cotransport. Klein, J.D., O'Neill, W.C. Am. J. Physiol. (1995) [Pubmed]
  17. 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]
  18. A single human myosin light chain kinase gene (MLCK; MYLK). Lazar, V., Garcia, J.G. Genomics (1999) [Pubmed]
  19. An MLCK-dependent window in late G1 controls S phase entry of proliferating rodent hepatocytes via ERK-p70S6K pathway. Bessard, A., Coutant, A., Rescan, C., Ezan, F., Frémin, C., Courselaud, B., Ilyin, G., Baffet, G. Hepatology (2006) [Pubmed]
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