contractile interaction between actin microfilaments and conventional smooth
muscle and non-muscle myosin II is regulated by phosphorylation of the 20kDa
regulatory light chains by myosin light chain kinase (MLCK). MLCK binds
both actin (Sellers
& Pato, 1984; Smith
et al, 1999;
Smith & Stull,
Hatch et al, 2001) and
myosin II. The MLCK activity is Ca2+-calmodulin dependent.
The Kd of MLCK for actin is 4mM
(Sellers & Pato,
1984), through an
N-terminus region that contains three repeats DFRxxL motifs (Smith
et al, 1999).
Image reconstruction indicates that MLCK binds the actin filament in a manner
that allows the simultaneous binding of the other major thin filament
components, calponin, tropomyosin etc. The binding site uniquely is
suggested to be on the outside of sub-domain 1 and perhaps the 228-232 region
(sub-domain 4) on another actin monomer. Two MLCK genes are expressed one
in muscle and the other in smooth muscle and non-muscle tissues. This
latter gene is expressed by differential splicing as a long and a shorter form (Herring
et al, 2000).
There is approximately one MLCK molecule for every 100 actin molecules in smooth
muscle (Hatch et
al, 2001), each
MLCK contains at least three of the DFRxxL motifs and so each molecule binds
three actins (Smith
et al, 1999; Smith
& Stull, 2000).
Birukov, K. G., Csortos, C., Marzilli, L.,
Dudek, S., Ma, S.-F., Bresnick, A. R., Verin, A. D., Cotter, R. J. & Garcia,
J. G. N. (2001) Differential regulation of alternatively spiced endothelial cell
myosin light chain kinase isoforms by p60Src., J.Biol.Chem. 276,
Hatch, V., Zhi, G., Smith, L., Stull, J. T.,
Craig, R. & Lehman, W. (2001) Myosin light chain kinase binding to a unique
site on F-actin revealed by three-dimensional image reconstruction., J. Cell
Biol. 154, 611-617.
Herring, B. P., Dixon, S. & Gallagher, P.
J. (2000) Smooth muscle myosin light chain kinase expression in cardiac and
skeletal muscle, Am.J.Physiol. 279, C1656-C1664.
Sellers, J.R. & Pato, M.D. (1984).
J.Biol.Chem. 259, 7740-7746.
Smith, L. & Stull, J. T.
(2000). “Myosin light chain kinase binding to actin filaments.” FEBS
letters 480(2-3), 298-300.
Smith, L., Su, X., Lin, P.-j., Zhi, G. &
Stull, J. T. (1999) Identification of a novel actin binding binding motif in
smooth muscle myosin light chain kinase., J. Biol.Chem. 274, 29433-29438.