Phosphorylation Dynamics in Smooth Muscle Myosin

Smooth muscle contraction is governed by the reversible phosphorylation of the myosin regulatory light chain (RLC), primarily at serine 19 and, under specific conditions, at threonine 18. Activation of myosin light chain kinase (MLCK) by the calcium–calmodulin complex triggers rapid phosphorylation of RLC, inducing a conformational shift that promotes actin binding and enhances the actin-activated MgATPase activity of the myosin motor. Dephosphorylation by myosin light chain phosphatase (MLCP) reverses this activation, allowing relaxation. Beyond MLCK and MLCP, auxiliary kinases such as protein kinase C can modulate additional sites on the light chain as well as on the heavy chain, fine-tuning contractile force and kinetics. These phosphorylation events alter filament stability, enzyme kinetics and filament-to-filament interactions, thereby controlling vascular tone, airway constriction and uterine contractility. Dysregulation of this dynamic equilibrium underlies a range of pathophysiological states, including hypertension, asthma and preterm labour. Advances in quantitative methods and structural analyses have begun to reveal the precise sequence of phosphorylation and dephosphorylation events, their interdependence and the resulting nanometre-scale rearrangements of the myosin head and tail domains, with significant implications for drug discovery and therapeutic modulation of smooth muscle tone.

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Phosphorylation Dynamics in Smooth Muscle Myosin publication trend

The graph below shows the total number of articles in phosphorylation dynamics in smooth muscle myosin across all publications each year (not limited to Nature Index journals).

Technical terms

Regulatory light chain (RLC): The 20 kDa accessory subunit of smooth muscle myosin whose phosphorylation state controls motor activity.

Myosin light chain kinase (MLCK): A Ca2+–calmodulin-dependent enzyme that phosphorylates RLC at serine 19 and threonine 18.

Myosin light chain phosphatase (MLCP): A heterotrimeric phosphatase that dephosphorylates RLC, leading to muscle relaxation.

Actin-activated MgATPase activity: The rate of ATP hydrolysis by myosin in the presence of actin, an index of motor activity.

Multiple reaction monitoring mass spectrometry (MRM-MS): A targeted proteomic technique for quantifying specific phosphorylated peptides with high sensitivity.

References

1. Tools and protocol for quantification of myosin phosphorylation with MRM-MS. MethodsX (2018).
2. Phosphorylation of smooth muscle myosin at two distinct sites by myosin light chain kinase.. Journal of Biological Chemistry (1985).
3. Identification, phosphorylation, and dephosphorylation of a second site for myosin light chain kinase on the 20,000-dalton light chain of smooth muscle myosin.. Journal of Biological Chemistry (1986).
4. Effects of phosphorylation of light chain residues threonine 18 and serine 19 on the properties and conformation of smooth muscle myosin.. Journal of Biological Chemistry (1988).
5. Effect of Multiple Phosphorylations of Smooth Muscle and Cytoplasmic Myosins on Movement in an in Vitro Motility Assay. Journal of Biological Chemistry (1989).
6. Phosphorylation of smooth muscle heavy meromyosin by calcium-activated, phospholipid-dependent protein kinase. The effect on actin-activated MgATPase activity.. Journal of Biological Chemistry (1983).