Myosin light chains initial

Phosphorylation of Myosin Light Chains Initiates Contraction of Smooth Muscle... 

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. 

Relaxation follows the drop in cytosolic calcium below the activation threshold, which initiates release of calcium from calmodulin, whereupon calmodulin dissociates from the kinase catalytic subunit. This results in loss of myosin light chain kinase activity. Under these conditions, the dephosphorylation of myosin light chains will be the predominant reaction. Consequently, actin and myosin will no longer interact and the muscle relaxes. 

Fig. 4. The temporal sequence of events when a resting strip of tracheal smooth muscle is activated by carbacholamine addition at 10 min. There is a transient rise in [Ca2+]c (—) followed by a transient increase in the content (—) of phosphorylated myosin light chains (MLC-P) which lead in turn to the initiation of force development (—). Increased force is sustained even though the content of MLC-P declines. Preceding the sustained phase of force maintenance, there is an increase in the phosphorylation of desmin (D-P), synemin (S-P), caldesmon (CD-P) and a number of low molecular weight cytosolic proteins (X-P). These remain phosphorylated throughout the sustained phase of the response during which there is a sustained increase in Ca2+ cycling across the plasma membrane which regulates the activity of the membrane-associated protein kinase C.

It has been established for several years that the major mechanism for regulation of contraction in smooth muscle is myosin phosphorylation (Hart-shorne, 1987). Phosphorylation of the two 20,000-dalton light chains of myosin (LC20) activates the actin-dependent ATPase activity of myosin and this initiates the contractile response. Dephosphorylated myosin is associated with relaxed muscle. In this scheme there are two key enzymes the myosin light chain kinase (MLCK) and the myosin light chain phosphatase (MLCP). Obviously a balance of these two activities determines the level of myosin phosphorylation. 

FIGURE 5 Comparison of amino acid sequence for myosin regulatory light chain proteins in different species. Cce, chicken cellular LC20-A, chicken adult smooth muscle LC20-B1, chicken embryonic smooth muscle Ram, rat aortic muscle Hsm, putative human smooth muscle. Amino acid residues are numbered starting at the Ser residue next to the initiator Met. A dot indicates identity of an amino acid residue with that in the top row. Reproduced with permission from Zavodny et al. (1990, Fig. 3, p. 937), Copyright 1994, American Heart Association. 

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