Structure and function of a calmodulin-dependent smooth muscle myosin light chain kinase.
In smooth muscle the Mr 20,000 light chain of myosin is phosphorylated by a calmodulin-dependent protein kinase. It consists of 2 subunits: calmodulin, an acidic protein of Mr 17,000 that binds 4 moles of Ca2+; and a larger protein of Mr circa 130,000. Activation of the kinase is dependent upon their association in the presence of Ca2+. Cyclic AMP-dependent protein kinase phosphorylation of the myosin light chain kinase occurs at 2 sites. It decreases the affinity of the kinase for calmodulin and a reduction in the rate of light chain phosphorylation occurs. The kinase has an overall asymmetric shape composed of a globular head and tail region for the skeletal muscle enzyme. Trypsin digestion of this kinase releases a fragment of Mr 36,000 from the globular region that contains the catalytic and calmodulin binding sites. Chymotrypsin digestion of the kinase from smooth muscle generates a fragment of Mr 80,000 that does not contain the calmodulin binding or cyclic AMP-dependent protein kinase phosphorylation sites. It is a Ca2+-independent form of the kinase that phosphorylates the light chain of myosin. These structural features indicate a regulatory role for the kinase in smooth muscle phosphorylation and contraction.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D002627:Chemistry, Physical; D000242:Cyclic AMP / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D046911:Macromolecular Substances; D008970:Molecular Weight; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000201:enzymology*; D009132:Muscles / Q000201:enzymology; D009219:Myosin-Light-Chain Kinase; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D013379:Substrate Specificity
D000596:Amino Acids; D002147:Calmodulin; D046911:Macromolecular Substances; D047428:Protein Kinase Inhibitors; D000242:Cyclic AMP; D011494:Protein Kinases; D009219:Myosin-Light-Chain Kinase; D000251:Adenosine Triphosphatases; D002118:Calcium