Regulation of Process Retraction and Cell Migration by EphA3 Is Mediated by the Adaptor Protein Nck1
Bibliographic record
Abstract
The Eph family of tyrosine kinase receptors and their ligands, the ephrins, participates in the regulation of a wide variety of biological functions under normal and pathological conditions. During embryonic development, interactions between the ligands and receptors define tissue boundaries, guide migrating axons, and regulate angiogenesis, as well as bone morphogenesis. These molecules have also been shown to modify neural activity in the adult nervous system and influence tumor progression. However, the molecular mechanisms underlying these diverse functions are not completely understood. In this study, we conducted a yeast two-hybrid screen to identify molecules that physically interact with Eph receptors using the cytoplasmic domain of EphA3 as "bait". This study identified Nck1 as a strong binding partner of EphA3 as assayed using both GST fusion protein pull down and co-immunoprecipitation techniques. The interaction is mediated through binding of the Nck1 SH2 domain to the phosphotyrosine residue at position 602 (Y602) of the EphA3 receptor. The removal of the SH2 domain or the mutation of the Y602 residue abolishes the interaction. We further demonstrated that EphA3 activation inhibits cell migration and process outgrowth, and these inhibiting effects are partially alleviated by dominant-negative Nck1 mutants that lack functional SH2 or SH3 domains, but not by the wild-type Nck1 gene. These results suggest that Nck1 interacts with EphA3 to regulate cell migration and process retraction.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Bench or experimental | high |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Bench or experimental | low |
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 | 0.000 | 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) | 0.000 | 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, unvalidatedLabeled directly by 2 models reading the full record.
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".