Redirecting tyrosine kinase signaling to an apoptotic caspase pathway through chimeric adaptor proteins
Bibliographic record
Abstract
Signal transduction pathways are typically controlled by protein-protein interactions, which are mediated by specific modular domains. One hypothetical use of such interaction domains is to generate new signaling pathways and networks during eukaryotic evolution, through the joining of distinct binding modules in novel combinations. In this manner, new polypeptides may be formed that make innovative connections among preexisting proteins. Adaptor proteins are specialized signaling molecules composed exclusively of interaction domains, that frequently link activated cell surface receptors to their intracellular targets. Receptor tyrosine kinases (RTKs) recruit adaptors, such as Grb2 and ShcA, that activate signaling pathways involved in growth and survival, whereas death receptors bind adaptors, such as Fadd, that promote apoptosis. To test the ability of interaction domains to create new signaling pathways, we have fused the phosphotyrosine recognition domains of Grb2 (Scr homology 2 domain) or ShcA (phosphotyrosine-binding domain) to the death effector domain of Fadd. We find that these chimeric adaptors can reroute mitogenic or transforming RTK signals to induce caspase activation and cell death. These hybrid adaptors can be used to selectively kill oncogenic cells in which RTK activity is deregulated.
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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) | 0.001 | 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 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".