Phosphorylation by casein kinase II alters the biological activity of calmodulin.
Calmodulin is the major intracellular Ca(2+)-binding protein, providing Ca(2+)-dependent regulation of numerous intracellular enzymes. The phosphorylation of calmodulin may provide an additional mechanism for modulating its function as a signal transducer. Phosphocalmodulin has been identified in tissues and cells, and calmodulin is phosphorylated both in vitro and in intact cells by various enzymes. Phosphorylation of calmodulin on serine/threonine residues by casein kinase II decreases its ability to activate both myosin-light-chain kinase and cyclic nucleotide phosphodiesterase. For myosin-light-chain kinase the primary effect is an inhibition of the Vmax. of the reaction, with no apparent change in the concentration at which half-maximal velocity is attained (K0.5) for either Ca2+ or calmodulin. In contrast, for phosphodiesterase, phosphorylation of calmodulin significantly increases the K0.5 for calmodulin without noticeably altering the Vmax. or the K0.5 for Ca2+. The higher the stoichiometry of phosphorylation of calmodulin, the greater the inhibition of calmodulin-stimulated activity for both enzymes. Therefore the phosphorylation of calmodulin by casein kinase II appears to provide a Ca(2+)-independent mechanism whereby calmodulin regulates at least two important target enzymes, myosin-light-chain kinase and cyclic nucleotide phosphodiesterase.
Sacks
D B
DB
Department of Pathology, Brigham and Women's Hospital, Boston, MA.
Davis
H W
HW
Williams
J P
JP
Sheehan
E L
EL
Garcia
J G
JG
McDonald
J M
JM
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002147:Calmodulin / Q000378:metabolism / Q000502:physiology*; D047390:Casein Kinase II; D002417:Cattle; D004789:Enzyme Activation; D007700:Kinetics; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011817:Rabbits; D013552:Swine
D002147:Calmodulin; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D009219:Myosin-Light-Chain Kinase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases