Coupling myosin light chain phosphorylation

The cAMP/Gs protein-coupled pathway stimulates adenylate (also known as adenylyl) cyclase, which catalyzes the formation of cAMP (Fig. 29.2). In VSM, unlike the heart, an increase in intracellular cAMP concentrations stimulated by a P2-adrenoceptor agonist, such as epinephrine or isoproterenol, binding to the p-receptor inhibits myosin light-chain phosphorylation, causing VSM relaxation. Therefore, drugs that increase cAMP (e.g., p2-adrenoceptor agonists, PDE3 phosphodiesterase inhibitors) cause vasodilation. On the other hand, stimulation of Gi protein inhibits adenylyl cyclase. 

The two heads of smooth muscle myosin interact cooperatively. Studies with the soluble two-headed HMM fragment clearly demonstrate that, whereas the phosphorylation of the two heads by myosin light chain kinase was random, phosphorylation of both heads was required for the MgATPase activity of either head to be activated by actin (Sellers et al., 1983 Per-sechini and Hartshorne, 1981). This cooperative activation of the two heads, coupled with the random phosphorylation, meant that at 50% phosphorylation (i.e., 1 mol Pj/mol HMM) there was only 25% of the... 

Pharmacomechanical coupling was primarily studied by measuring [Ca +J and myosin regulatory light chain phosphorylation in intact and skinned smooth muscle. Several groups found that stimuli increased... 

Di Salvo J Nelson SR, Kaplan N (1997) Protein tyrosine phosphorylation in smooth muscle a potential coupling mechanism between receptor activation and intracellular calcium. Proc Soc Bxp Biol Med 214 285-301 Erdodi F, Ito M, Hartshome DJ. (1996) Myosin light chain phosphatase. In Bdrany M (ed) Biochemistry of smooth muscle contraction. Academic Press, San Diego, pp 13M42... 

Sah, V.P, Seasholtz, T.M., Sagi, S.A. et al. (2000). The role of Rho in G protein-coupled receptor signal transduction. Ann. Rev. Pharmacol. Toxicol. 40, 459-489. Saitoh, T, Takemura, S., Ueda, K. et al. (2001). Differential localization of nonmuscle myosin 11 isoforms and phosphorylated regulatory light chains in human MRG-5 fibroblasts. FEBS Lett. 509, 365-369. 

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