Myosin Light Chain Kinase Phosphorylation: Regulation of the Ca²⁺ Sensitivity of Contractile Elements

Abstract

Cyclic AMP-dependent protein kinase phosphorylates myosin light chain kinase purified from gizzard smooth muscle (Adelstein et al., 1978). In the absence of Ca²⁺/calmodulin, 2 sites (sites A and B) are phosphorylated and the concentration of Ca²⁺/calmodulin required for half-maximal activation (KcaM) increases 10 fold (Conti and Adelstein, 1981). In the presence of Ca²⁺/calmodulin, phosphate is incorporated into site B with no effect on myosin light chain kinase activity. As shown in Figure 1, site A is near the calmodulin binding domain whereas site B is more toward the c-terminus. Similar observations on kinase phosphorylation have been made with myosin light chain kinases purified from mammalian smooth muscles including trachea (Miller et al., 1983), stomach (Walsh et al., 1982), myometrium (Higashi et al., 1983), aorta (Vallet et al., 1981), and carotid artery (Bhalla et al., 1982). It has been proposed that phosphorylation of site A by cyclic AMP-dependent protein kinase could decrease the extent of myosin light chain kinase activation with a resultant decrease in myosin light chain phosphorylation and inhibition of contraction (Conti and Adelstein, 1981).