Role of MEKK2 Phosphorylation at Threonine 263 on SMYD3-Mediated Methylation of Lysine 260
Bibliographic record
Abstract
MEKK2 is a protein serine/threonine-kinase involved in the activation of many MAP-kinase signalling pathways. In a previous study, SMYD3-mediated methylation at K260 of MEKK2 was demonstrated to promote aberrant input downstream of oncogenic Ras-signaling, promoting Ras-driven PDAC and LAC progression. Our lab has previously characterized the role of MEKK2 phosphorylation at T283 and has recently discovered a novel second phosphorylation site at T263. We show that together, these sites form the bipartite binding group for 14-3-3 adapter proteins. This study focuses on characterizing T263 and T283 as regulatory phosphosites in K260 methylation and implicates 14-3-3 as a promoting factor in facilitating SMYD3-mediated methylation at K260. Our findings provide a potential mechanism of MEKK2 oncogenic function, whereby 14-3-3 preserves phosphorylation at T263 and T283, together promoting K260 methylation and MEKK2 activation. Our study characterizes T263 and T283 of MEKK2 and 14-3-3 phosphoadapter proteins as potential therapeutic targets in PDAC and LAC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".