Myosin phosphorylation/dephosphorylation and regulation of airway smooth muscle contractility.
Airway smooth muscles contract due to the activation of a highly sophisticated signal transduction mechanism. Signal transduction in muscle must include 1) a mechanism for converting chemical energy (i.e., ATP) into mechanical work (energy transduction) and 2) a mechanism for integrating the response to multiple stimuli (signal integration). In smooth and striated muscles, ATP hydrolysis due to the cyclic interaction of actin and myosin is the final site for both energy transduction and signal integration. There is growing consensus that this interaction in smooth muscles is regulated by the phosphorylation/dephosphorylation of the 20-kDa light chain of smooth muscle myosin. By phosphorylation/dephosphorylation we mean the enzyme-catalyzed transfer of the terminal phosphate of ATP to a serine or threonine residue on a protein, by a class of enzymes known as protein kinases, with the formation of a covalent phosphoester linkage and the enzyme-catalyzed removal of the phosphate group by phosphoprotein phosphatases. Smooth muscles contain many protein kinases and phosphatases, and the research emphasis on the regulation of smooth muscle contraction has focused on how these enzymes act individually and in concert to regulate the actin-myosin interaction. This review will describe the biochemical and physiological experiments that have been performed to understand the role of myosin phosphorylation/dephosphorylation in regulating smooth muscle contraction. Although data from studies on vascular and other smooth muscles will be summarized, this review will focus on studies performed on airway smooth muscle. More detailed reviews of studies on nonairway smooth muscles can be found in Refs. 47 and 79.
de Lanerolle
P
P
Department of Physiology, University of Illinois, Chicago 60680.
Paul
R J
RJ
D000818:Animals; D005544:Forecasting; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D014132:Trachea / Q000502:physiology*
D009712:Nucleotides, Cyclic; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D009218:Myosins