Molecular Mechanisms Underlying Phosphorylation-mediated Regulation of the KRAS Oncoprotein
Bibliographic record
Abstract
RAS is a small GTPase protein that cycles between GTP and GDP-loaded states to regulate vital eukaryotic cellular functions such as proliferation. Mutations in RAS account for approximately 30% of human cancers, however, it has remained ‘undruggable’ largely due to our incomplete understanding of the mechanisms governing its activity. Recently, we discovered a novel paradigm of RAS regulation in which Src-induced phosphorylation significantly impairs the entire GTPase cycle, including RAS interactions with downstream effector molecules. However, the mechanisms underlying Src-mediated regulation of RAS remain unclear. Here, using various in vitro biochemical and functional assays, the relationship between KRAS phosphorylation and RAF effector binding was analyzed. Results show that effector binding impedes phosphorylation of KRAS via Src, indicating that this modification alone is insufficient to displace RAF from KRAS, as previously expected. This valuable insight into RAS signalling may contribute to the development of novel therapeutics targeting this pathway of oncogenesis.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".