Control of cross-bridge cycling by myosin light chain phosphorylation in mammalian smooth muscle.
This review focuses on experiments in which the single turnover of myosin-bound ADP is used to characterize the regulation of the cross-bridge cycle by myosin light chain phosphorylation in mammalian smooth muscle. Under isometric conditions, at rest, when the myosin light chain is not phosphorylated, myosin cycles very slowly (about 0.004 s-1), while phosphorylation of the light chain results in a 50-fold increase in cycling rate of 0.2 s-1. Experiments consistently show that some myosin does not increase its cycling rate although its light chain is phosphorylated. Studies at low levels of myosin light chain phosphorylation show that phosphorylation also induces an increase in the cycling rate of unphosphorylated myosin. The fast cycling phosphorylated myosin is the main determinant of suprabasal myosin ATPase activity, while the cycling rate of cooperatively activated unphosphorylated myosin is slow and appears to depend on the extent of phosphorylation of the entire thick filament. Single turnover experiments measuring the rate of phosphorylation and dephosphorylation of myosin light chain show that the turnover of light chain phosphate can be very rapid (0.3-0.4 s-1) at suprabasal calcium concentrations. The expected effect of such a rapid turnover of light chain phosphorylation on the turnover of myosin-bound ADP is not observed. The effects of low levels of myosin light chain phosphorylation on the single turnover of myosin suggest that the same small pool of myosin remains phosphorylated for relatively long periods of time rather than the entire pool of myosin spending a small fraction of its cycle time in the phosphorylated state.
Butler
T M
TM
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Siegman
M J
MJ
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006801:Humans; D008322:Mammals / Q000502:physiology*; D009130:Muscle, Smooth / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D018994:Myosin Light Chains / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation
D018994:Myosin Light Chains; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate