Cross-bridge cycling phosphorylation

At this site, creatine kinase catalyses the phosphorylation of ADP by phosphocreatine with the production of ATP which, in turn, is used by the energy-requiring process that is, the cross-bridge cycle (Chapter 13). 

Figure 22.12 Regulation of actin-myosin interaction in smooth muscle via the light-chain kinase and phosphatase and effect on blood pressure. ions bind to calmodulin and the complex stimulates the conversion of inactive myosin light chain kinase (MLCK) to active MLCK which then phosphorylates the light chain. This results in activation of the cross-bridge cycle. The overall effect is vasoconstriction of the arteriole, which increases blood pressure.

Dillon, P.F., Aksoy, M.O., Driska, S.P. and Murphy, RA. (1981). Myosin phosphorylation and the cross-bridge cycle in smooth muscle. Science (Wash). DC211, 495-497. 

The more classic pathway of smooth muscle contractile activation is illustrated in the right-hand side of this panel, where activation leads to an increase in intracellular ionized calcium concentration ([Ca +jj) by virtue of Ca + entry through channels or exchangers (Lyu et al, 1992 van Breemen et al, 1985 Khalil et al, 1987) or the release of Ca2+ from the sarcoplasmic reticulum. [Ca +J in combination with calmodulin activates myosin light chain (MLC) kinase to cause phosphorylation of the 20-kDa MLC, which in turn results in increased actin-activated myosin AT-Pase activity, increase cross-bridge cycling velocity, and, as a result, an increase in contractile force (Aksoy et al, 1976 Sobieszek, 1977). 

The exchange of the covalently bound phosphate of LC20 during contraction (see Section V) supports a relationship between LC20 phosphorylation and cross-bridge cycling rate. 

The current research priorities include elucidation of the in vivo function of proteins such as CD and CP that need not involve cross-bridge cycling, and resolving the physiological relevance of the experimental situations in which LC20 phosphorylation does not explain contraction. Another potentially fertile topic is identification of mechanisms that modulate MLCK and MLCP activities and, of equal importance, establishing their in vivo significance. 

Regulation by myosin phosphorylation, which is of particular importance for smooth muscle, is a feature of the less specialized actomyosin contractile systems. In striated muscle it would appear that light chain phosphorylation has been relegated to a modulatory role in the cross-bridge cycle, and response to stimulation has been accelerated by the evolution of the troponin system located in the I filament. The consequence is that the rapid binding of calcium to one molecule of troponin C renders seven actin molecules available to interact with as many heads of myosin molecules as they can accommodate. In smooth muscle, binding of cal-... 

One consequence of the simulations using the four state model (Hai and Murphy 1988a, Hai and Murphy 1992) was that the dependence of ATPase on force was non-linear and increased steeply at higher force levels, due to increased rates of both cross-bridge cycling and LC20 phosphorylation turnover. This result was found to be at variance with earlier data on ATP... 

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