Phosphorylation of myosin light chain kinase: a cellular mechanism for Ca2+ desensitization.
Phosphorylation of the regulatory light chain of myosin by the Ca2+/calmodulin-dependent myosin light chain kinase plays an important role in smooth muscle contraction, nonmuscle cell shape changes, platelet contraction, secretion, and other cellular processes. Smooth muscle myosin light chain kinase is also phosphorylated, and recent results from experiments designed to satisfy the criteria of Krebs and Beavo for establishing the physiological significance of enzyme phosphorylation have provided insights into the cellular regulation and function of this phosphorylation in smooth muscle. The multifunctional Ca2+/calmodulin-dependent protein kinase II phosphorylates myosin light chain kinase at a regulatory site near the calmodulin-binding domain. This phosphorylation increases the concentration of Ca2+/calmodulin required for activation and hence increases the Ca2+ concentrations required for myosin light chain kinase activity in cells. However, the concentration of cytosolic Ca2+ required to effect myosin light chain kinase phosphorylation is greater than that required for myosin light chain phosphorylation. Phosphorylation of myosin light chain kinase is only one of a number of mechanisms used by the cell to down regulate the Ca2+ signal in smooth muscle. Since both smooth and nonmuscle cells express the same form of myosin light chain kinase, this phosphorylation may play a regulatory role in cellular processes that are dependent on myosin light chain phosphorylation.
Stull
J T
JT
Department of Physiology, University of Texas Southwestern Medical Center at Dallas 75235.
Tansey
M G
MG
Tang
D C
DC
Word
R A
RA
Kamm
K E
KE
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000201:enzymology / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000201:enzymology / Q000502:physiology; D009219:Myosin-Light-Chain Kinase / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation
D002147:Calmodulin; D009219:Myosin-Light-Chain Kinase; D002118:Calcium