Investigating the anionic phospholipid regulation of diacylglycerol kinase epsilon
Bibliographic record
Abstract
Mammalian diacylglycerol kinases (DGKs) form critical links in cell signaling pathways by catalyzing the phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PA); regulating the levels of these two essential second messengers in the cell. The epsilon isoform of DGK (DGKε), possesses the simplest primary structure of any DGK isoform, yet is unique in its inhibition by anionic phospholipids such as PA. The molecular mechanisms underlying this unique feature of DGKε are unknown. Here we show that there is a combined acyl chain specificity in the PA inhibition of DGKε, favouring a combination of an arachidonyl sn ‐2 and a stearoyl sn ‐1 acyl chain. These results contrast to those of previous reports in which an arachidonyl‐DAG specific isoform of DGK did not exhibit PA acyl chain specific inhibition. Also, deletion of DGKε's cationic cluster retains its PA acyl chain specific inhibition, a region previously hypothesized as a candidate for PA binding. Overall, these results suggest that the PA acyl chain specific inhibition of DGKε occurs through a binding site within DGKε with a definite shape that is not found in DGKε's cationic cluster. This work is funded by NSERC and the NIH.
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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) | 0.000 | 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".