Myosin Regulatory Light Chain Diphosphorylation Slows Relaxation of Arterial Smooth Muscle
Bibliographic record
Abstract
The principal signal to activate smooth muscle contraction is phosphorylation of the regulatory light chains of myosin (LC 20 ) at Ser 19 by Ca 2+ /calmodulin-dependent myosin light chain kinase. Inhibition of myosin light chain phosphatase leads to Ca 2+ -independent phosphorylation at both Ser 19 and Thr 18 by integrin-linked kinase and/or zipper-interacting protein kinase. The functional effects of phosphorylation at Thr 18 on steady-state isometric force and relaxation rate were investigated in Triton-skinned rat caudal arterial smooth muscle strips. Sequential phosphorylation at Ser 19 and Thr 18 was achieved by treatment with adenosine 5′- O -(3-thiotriphosphate) in the presence of Ca 2+ , which induced stoichiometric thiophosphorylation at Ser 19 , followed by microcystin (phosphatase inhibitor) in the absence of Ca 2+ , which induced phosphorylation at Thr 18 . Phosphorylation at Thr 18 had no effect on steady-state force induced by Ser 19 thiophosphorylation. However, phosphorylation of Ser 19 or both Ser 19 and Thr 18 to comparable stoichiometries (0.5 mol of P i /mol of LC 20 ) and similar levels of isometric force revealed differences in the rates of dephosphorylation and relaxation following removal of the stimulus: t ½ values for dephosphorylation were 83.3 and 560 s, and for relaxation were 560 and 1293 s, for monophosphorylated (Ser 19 ) and diphosphorylated LC 20 , respectively. We conclude that phosphorylation at Thr 18 decreases the rates of LC 20 dephosphorylation and smooth muscle relaxation compared with LC 20 phosphorylated exclusively at Ser 19 . These effects of LC 20 diphosphorylation, combined with increased Ser 19 phosphorylation (Ca 2+ -independent), may underlie the hypercontractility that is observed in response to certain physiological contractile stimuli, and under pathological conditions such as cerebral and coronary arterial vasospasm, intimal hyperplasia, and hypertension. Background: The regulatory light chains of smooth muscle myosin are phosphorylated at Ser 19 and Thr 18 . Results: Phosphorylation at Thr 18 does not increase force elicited by Ser 19 phosphorylation, but reduces the rate of relaxation. Conclusion: Diphosphorylation slows relaxation compared with monophosphorylation at Ser 19 . Significance: Knowledge of the functional effects of myosin diphosphorylation is important for understanding the underlying causes of hypercontractility.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".