20. Discovery of Novel Proteins Involved the Insulin/IGF-1 Signalling Pathway
Bibliographic record
Abstract
The insulin/insulin growth factor-1 (IGF-1) signalling (IIS) pathway plays a key role in metabolism, growth and development. Though research has elucidated aspects of this pathway, it is not fully characterized or understood. A better understanding of the pathway will give insight into related diseases such as cancer. To discover novel proteins involved in the IIS pathway, the C. elegans worm was used due to the homology its insulin/IGF-1 receptor shares with that of humans. To identify novel protein interactions with the insulin/IGF-1 receptor, we performed a yeast two-hybrid screen using a library of worm proteins. We found several separate interactions with the worm homolog of the HSP90 protein. To support the involvement of HSP90 in the IIS pathway, we studied the phenotypes of worm strains with a mutant form of HSP90. They showed a similar phenotype to those that have a mutant form of the insulin/IGF-1 receptor, inappropriately entering a developmental stage known as dauer. This strongly suggests the involvement of HSP90 in the IIS pathway. Based on previous research, we hypothesized the interaction between HSP90 and the insulin/IGF-1 receptor may allow it to bind other proteins. Thus, we performed a modified yeast two-hybrid screen to identify proteins which interact with the receptor in the presence of HSP90. The screen identified 15 interactions, many more than with the insulin/IGF-1 receptor alone, supporting this hypothesis. Overall, we provide evidence of a novel interaction with insulin/IGF-1 receptor, suggesting HSP90 may be a potential target for developing therapies for IIS pathway related diseases.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".