Myosin light-chain

In the presence of calcium, the primary contractile protein, myosin, is phosphorylated by the myosin light-chain kinase initiating the subsequent actin-activation of the myosin adenosine triphosphate activity and resulting in muscle contraction. Removal of calcium inactivates the kinase and allows the myosin light chain to dephosphorylate myosin which results in muscle relaxation. Therefore the general biochemical mechanism for the muscle contractile process is dependent on the avaUabUity of a sufficient intraceUular calcium concentration. 

Figure 14.14 Sci ematic diagram of the myosin molecule, comprising two heavy chains (green) that form a coiled-coil tail with two globular heads and four light chains (gray) of two slightly differing sizes, each one bound to each heavy-chain globular head.

Figure 14.15 Stmcture of the SI fragment of chicken myosin as a Richardson diagram (a) and a space-filling model (b). The two light chains are shown in magenta and yellow. The heavy chain is colored according to three proteolytic fragments produced by trypsin a 25-kDa N-terminal domain (green) a central 50-kDa fragment (red) divided by a cleft into a 50K upper and a 50K lower domain and a 20-kDa C-terminal domain (blue) that links the myosin head to the coiled-coil tail. The 50-kDa and 20-kDa domains both bind actin, while the 25-kDa domain binds ATP. [(b) Courtesy of 1. Rayment.]...

Myosin light-chain kinase (MLCK) —ia[Pg.467]

Smooth muscle contractions are subject to the actions of hormones and related agents. As shown in Figure 17.32, binding of the hormone epinephrine to smooth muscle receptors activates an intracellular adenylyl cyclase reaction that produces cyclic AMP (cAMP). The cAMP serves to activate a protein kinase that phosphorylates the myosin light chain kinase. The phosphorylated MLCK has a lower affinity for the Ca -calmodulin complex and thus is physiologically inactive. Reversal of this inactivation occurs via myosin light chain kinase phosphatase. 

The ETa receptor activates G proteins of the Gq/n and G12/i3 family. The ETB receptor stimulates G proteins of the G and Gq/11 family. In endothelial cells, activation of the ETB receptor stimulates the release of NO and prostacyclin (PGI2) via pertussis toxin-sensitive G proteins. In smooth muscle cells, the activation of ETA receptors leads to an increase of intracellular calcium via pertussis toxin-insensitive G proteins of the Gq/11 family and to an activation of Rho proteins most likely via G proteins of the Gi2/i3 family. Increase of intracellular calcium results in a calmodulin-dependent activation of the myosin light chain kinase (MLCK, Fig. 2). MLCK phosphorylates the 20 kDa myosin light chain (MLC-20), which then stimulates actin-myosin interaction of vascular smooth muscle cells resulting in vasoconstriction. Since activated Rho... 

This kinase specifically phosphorylates the regulatory light chain of myosin after activation by calcium-calmodulin. Several isozymes of approximately 135 kDa exist. 

Smooth muscle myosin contains two myosin light chains. Phosphorylation of the regulatory light chain by myosin light chain kinase is a mandatory step to induce contraction. 

Skeletal muscle myosin-Il was first purified in the 1930s and has been extensively studied since (Engelhardt and Ljubimova, 1939). Myosin-II is a dimer composed of two molecules of myosin joined by intertwined, filamentous tails, with each monomer containing two pairs of light chains (Figure 2) (Adelstein and... 

The regulatory light chains from vertebrate forms of myosin-II undergo reversible phosphorylation by a calmodulin dependent enzyme called myosin light chain... 

Myosin-II phosphorylation is also an important mechanism for regulating myosin assembly in nonmuscle and smooth muscle cells (Kom and Hammer, 1988). For example, myosin-II ixomAcanthamoeba is more soluble when the heavy chain is phosphorylated compared to the unphosphorylated species. Similarly, phosphorylation of the light chains of vertebrate smooth muscle and nonmuscle myosin-II affects filament formation by these myosins. These myosins undergo a... 

Myosin-I molecules have several IQ sequences on or near the head and have light chains associated with them (Cheney and Mooseker, 1992 Cheney et al., 1993). Frequently, the light chains appear to be calmodulin molecules and some myosin-I molecules can bind three to four molecules of calmodulin at one time. Brush-border and adrenal myosin-I also bind calmodulin. Acanthamoeba myosin-I has a light chain that can be removed, in vitro, without adversely affecting the ATPase activity or the heavy chain phosphorylation (Korn and Hammer, 1988). The role of these calmodulin molecules in regulating myosin-I is complex and poorly understood. One possibility is that the calmodulin molecules dissociate from the heavy chains when calcium binds to the calmodulin, thereby imparting greater flexibility to the head of the myosin-I molecules. 

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