NCK adaptor proteins regulate clathrin-coated pit dynamics and EGF-stimulated PI3K-Akt signaling
Bibliographic record
Abstract
Abstract The epidermal growth factor (EGF) receptor (EGFR) promotes cell growth, proliferation, and survival. EGF binding to EGFR activates receptor kinase activity, leading to membrane recruitment of class IA phosphoinositide-3-kinase (PI3K), thus activating Akt signaling. Clathrin-coated pits (CCPs) are plasma membrane endocytic structures that are enriched in signaling intermediates and regulate in EGF-stimulated Akt activation. The mechanisms and impact of recruitment of certain signaling molecules within the PI3K-Akt pathway to CCPs remains poorly understood. Using total internal reflection fluorescence microscopy (TIRFM), we observed that the adaptor proteins Nck1 and Nck2 are enriched within CCPs and regulate early CCP formation and maturation. Nck1 and Nck2 each support EGF-stimulated Akt phosphorylation. Notably, EGF stimulation triggers Nck-dependent enrichment of PI3K within CCPs, and perturbation of Nck adaptors suppressed cell proliferation and survival. This study identifies novel functions for Nck adaptor proteins in EGFR-mediated recruitment of PI3K-Akt signals within CCPs, Akt activation, and cell physiology.
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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) | 0.001 | 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".