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MYLK  -  myosin light chain kinase

Gallus gallus

 
 
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Disease relevance of MYLK

 

High impact information on MYLK

  • A polyclonal antibody against myosin light chain kinase (MLCK) of chicken gizzard recognized a 130 kd peptide of bullfrog sympathetic ganglia as MLCK [4].
  • Sellers (1981. J. Biol. Chem. 256:9274-9278), Limulus myosin, incubated with partially purified chicken gizzard myosin light chain kinase (MLCK) and [gamma 32P]-ATP, binds 2 mol phosphate/mole protein [5].
  • Ca++-independent contraction was obtained by preincubation in Ca++ and ATP gamma S, or by addition of trypsin-treated myosin light chain kinase (MLCK) that no longer requires Ca++ for activation [6].
  • The TATA box, the transcription initiation site, and the first 109 nucleotides of the 5' noncoding region of the KRP mRNA correspond to an MLCK gene intron sequence [7].
  • Both KRP and MLCK are produced in the same adult chicken tissue in relatively high abundance from a single contiguous stretch of genomic DNA and utilize the same reading frame and common exons to produce distinct mRNAs (2.7 and 5.5 kb, respectively) that encode proteins with dissimilar biochemical functions [7].
 

Biological context of MYLK

  • The nonmuscle/smooth muscle myosin light chain kinase (MLCK) and the kinase related protein (KRP) that lacks protein kinase activity are myosin II binding proteins encoded in the vertebrate genome by a true gene within a gene relationship [8].
  • The telokin cDNA coded 157 amino acid residues which were completely identical to the C-terminal portion of the amino acid sequence of chicken gizzard MLCK [9].
  • Second, one- and two-dimensional peptide maps have revealed that the site of phosphorylation by the MLCK kinase of mitotic cells differs from those by these known kinases [10].
  • MLCK-(480-501) potently inhibited MLCK (IC50 = 0.25 microM) and also strongly inhibited both PKC and CaMK-II (IC50 = 1.4 and 1.7 microM, respectively) [11].
  • These data support the contention that CaM and MLCK are constitutively expressed but vary as a function of cell cycle [12].
 

Anatomical context of MYLK

  • Parent MLCK exhibited both calcium ion (Ca2+) and calmodulin (Ca2+/CaM)-sensitive and Ca2+/CaM-insensitive binding to actin filaments [13].
  • Smooth muscle myosin light chain kinase (MLCK) is stable in the presence of Ca2+/calmodulin and does not undergo inactivation as reported for skeletal muscle MLCK (Kennelly, P.J., Starovasnik, M.A., Edelman, A.M., and Krebs, E.G. (1990) J. Biol. Chem. 265, 1742-1749) [14].
  • Cell cytosol preparations from mitotic HeLa cells exhibit a kinase activity that phosphorylates myosin light chain kinase (MLCK) [10].
  • Furthermore, wortmannin also inhibited both the phosphorylation of myosin light chain and the contraction in rat thoracic aorta stimulated with KCl, which indicates the effectiveness of the compound in the cellular level as an MLCK inhibitor [15].
  • Small changes were noted in both CaM and MLCK RNAs during primary stimulation when oviduct cells are actively dividing [12].
 

Associations of MYLK with chemical compounds

  • Changes in myosin light chain kinase (MLCK) and calmodulin (CaM) mRNAs have been evaluated during estrogen-mediated differentiation of the chicken oviduct [12].
  • The inhibitory action of Ro 22-4839 on the contractile system of the smooth muscle was demonstrated directly by its inhibition of chicken gizzard MLCK [16].
  • Partially purified MLCK from rat aorta migrated as a 145 kDa protein on SDS/polyacrylamide gels [1].
  • A protein kinase phosphorylation site in chicken gizzard myosin light chain kinase (MLCK) has been identified, and a synthetic peptide analogue of this site has been shown to be a high-affinity calmodulin binding peptide as well as a substrate for cyclic AMP dependent protein kinase [17].
  • Vrolix, Raeymaekers, Wuytack, Hofmann & Casteels [(1988) Biochem. J. 255, 855-863] have reported the presence of a 130 kDa cyclic GMP-dependent protein kinase substrate protein in the membrane fraction of pig aorta or stomach, and suggested that it may be myosin light chain kinase (MLCK) [1].
 

Enzymatic interactions of MYLK

  • MLCK is a calmodulin (CaM) regulated protein kinase that phosphorylates the light chain of myosin II [18].
 

Analytical, diagnostic and therapeutic context of MYLK

  • A synthetic peptide corresponding to an inhibitory domain of MLCK (Ala783-Gly804) was applied intracellularly to isolated sympathetic neurons during whole-cell recordings of ionic currents [4].
  • Peptide mapping and phosphoamino acid analyses revealed that the primary phosphorylation site of MLC by Rho-kinase was Ser-19, which is the site phosphorylated by MLC kinase [19].
  • Immunoblotting the partially purified rat aortic MLCK with antibody to bovine tracheal MLCK identified rat aortic MLCK (145 kDa) and a corresponding 145 kDa protein in the particulate fraction of cultured rat aortic smooth muscle cells, but did not detect the 132 kDa protein [1].
  • The interaction of calmodulin with a synthetic peptide based on this sequence was characterized by using circular dichroism and fluorescence spectroscopies and inhibition of calmodulin activation of MLCK [17].
  • 7. Gizzard Ca2+-independent LC20 kinase could be separated from MLCK by differential extraction from myofilaments and by CaM affinity chromatography [20].

References

  1. The smooth muscle 132 kDa cyclic GMP-dependent protein kinase substrate is not myosin light chain kinase or caldesmon. Sarcevic, B., Robinson, P.J., Pearson, R.B., Kemp, B.E. Biochem. J. (1990) [Pubmed]
  2. Boundary of the autoinhibitory region of smooth muscle myosin light-chain kinase. Yano, K., Araki, Y., Hales, S.J., Tanaka, M., Ikebe, M. Biochemistry (1993) [Pubmed]
  3. MS-282a and MS-282b, new inhibitors of calmodulin-activated myosin light chain kinase from Streptomyces tauricus ATCC 27470. Nakanishi, S., Kita, K., Uosaki, Y., Yoshida, M., Saitoh, Y., Mihara, A., Kawamoto, I., Matsuda, Y. J. Antibiot. (1994) [Pubmed]
  4. Myosin light chain kinase occurs in bullfrog sympathetic neurons and may modulate voltage-dependent potassium currents. Akasu, T., Ito, M., Nakano, T., Schneider, C.R., Simmons, M.A., Tanaka, T., Tokimasa, T., Yoshida, M. Neuron (1993) [Pubmed]
  5. Effects of phosphorylation by myosin light chain kinase on the structure of Limulus thick filaments. Levine, R.J., Chantler, P.D., Kensler, R.W., Woodhead, J.L. J. Cell Biol. (1991) [Pubmed]
  6. Regulation of contraction and thick filament assembly-disassembly in glycerinated vertebrate smooth muscle cells. Cande, W.Z., Tooth, P.J., Kendrick-Jones, J. J. Cell Biol. (1983) [Pubmed]
  7. Structure and expression of a calcium-binding protein gene contained within a calmodulin-regulated protein kinase gene. Collinge, M., Matrisian, P.E., Zimmer, W.E., Shattuck, R.L., Lukas, T.J., Van Eldik, L.J., Watterson, D.M. Mol. Cell. Biol. (1992) [Pubmed]
  8. Multiple gene products are produced from a novel protein kinase transcription region. Watterson, D.M., Collinge, M., Lukas, T.J., Van Eldik, L.J., Birukov, K.G., Stepanova, O.V., Shirinsky, V.P. FEBS Lett. (1995) [Pubmed]
  9. Molecular cloning of the chicken gizzard telokin gene and cDNA. Yoshikai, S., Ikebe, M. Arch. Biochem. Biophys. (1992) [Pubmed]
  10. Mitosis-specific phosphorylation of myosin light chain kinase. Hosoya, H., Yamashiro, S., Matsumura, F. J. Biol. Chem. (1991) [Pubmed]
  11. Specificities of autoinhibitory domain peptides for four protein kinases. Implications for intact cell studies of protein kinase function. Smith, M.K., Colbran, R.J., Soderling, T.R. J. Biol. Chem. (1990) [Pubmed]
  12. Hormonal regulation of a chicken oviduct messenger ribonucleic acid that shares a common domain with gizzard myosin light chain kinase. Russo, M.A., Guerriero, V., Means, A.R. Mol. Endocrinol. (1987) [Pubmed]
  13. The structure and function of the actin-binding domain of myosin light chain kinase of smooth muscle. Ye, L.H., Hayakawa, K., Kishi, H., Imamura, M., Nakamura, A., Okagaki, T., Takagi, T., Iwata, A., Tanaka, T., Kohama, K. J. Biol. Chem. (1997) [Pubmed]
  14. Role of the pseudosubstrate sequence in smooth muscle myosin light chain kinase thermal stability. Faux, M.C., Pearson, R.B., Mitchelhill, K.I., Kemp, B.E. J. Biol. Chem. (1993) [Pubmed]
  15. Wortmannin, a microbial product inhibitor of myosin light chain kinase. Nakanishi, S., Kakita, S., Takahashi, I., Kawahara, K., Tsukuda, E., Sano, T., Yamada, K., Yoshida, M., Kase, H., Matsuda, Y. J. Biol. Chem. (1992) [Pubmed]
  16. Selective calmodulin inhibition toward myosin light chain kinase by a new cerebral circulation improver, Ro 22-4839. Nakajima, T., Katoh, A. Mol. Pharmacol. (1987) [Pubmed]
  17. Calmodulin binding domains: characterization of a phosphorylation and calmodulin binding site from myosin light chain kinase. Lukas, T.J., Burgess, W.H., Prendergast, F.G., Lau, W., Watterson, D.M. Biochemistry (1986) [Pubmed]
  18. Organization of the genetic locus for chicken myosin light chain kinase is complex: multiple proteins are encoded and exhibit differential expression and localization. Birukov, K.G., Schavocky, J.P., Shirinsky, V.P., Chibalina, M.V., Van Eldik, L.J., Watterson, D.M. J. Cell. Biochem. (1998) [Pubmed]
  19. Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). Amano, M., Ito, M., Kimura, K., Fukata, Y., Chihara, K., Nakano, T., Matsuura, Y., Kaibuchi, K. J. Biol. Chem. (1996) [Pubmed]
  20. Ca2+-independent phosphorylation of myosin in rat caudal artery and chicken gizzard myofilaments. Weber, L.P., Van Lierop, J.E., Walsh, M.P. J. Physiol. (Lond.) (1999) [Pubmed]
 
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