Cleavage of glycogen synthase kinase‐3beta by matrix metalloproteinase‐2 enhances its kinase activity
Bibliographic record
Abstract
Matrix metalloproteinase (MMP)‐2 is localized to the sarcomere of cardiomyocytes and contributes to myocardial ischemia‐reperfusion injury by degrading sarcomeric and cytoskeletal proteins. Oxidative stress mediates its damaging effects through activation of MMP‐2 within the cardiomyocyte and subsequent proteolysis of susceptible intracellular targets. Glycogen synthase kinase (GSK)‐3β is involved in growth, death & metabolism and susceptible to proteolytic cleavage. We determined whether GSK‐3β is a proteolytic substrate of MMP‐2 and how this cleavage affects its kinase activity. Incubation of MMP‐2 and GSK‐3β resulted in a time‐ and concentration‐dependant cleavage of GSK‐3β with significant increase in GSK‐3β kinase activity. Dephosphorylation of GSK‐3β with λ‐phosphatase prevented MMP‐2 mediated augmented kinase activity. H 2 O 2 treated H9c2 cardiomyoblasts showed increased levels and activity of MMP‐2 accompanied by significant reduction in GSK‐3β protein levels and increased kinase activity. The data indicate that GSK‐3β is a target of MMP‐2 and that its cleavage by MMP‐2 enhances GSK‐3β kinase activity. GSK‐3β dephosphorylation studies suggest that MMP‐2 may cleave off the inhibitory serine‐9 residue. This MMP‐2 mediated augmentation of GSK‐3β kinase activity may contribute to cardiac dysfunction as a result of myocardial oxidative stress injury. This work was supported by CIHR.
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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) | 0.001 | 0.001 |
| 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 | 0.001 |
| 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".