Nck1 depletion induces activation of the PI3K/Akt pathway by attenuating PTP1B protein expression
Bibliographic record
Abstract
BACKGROUND: Activation of the PI3K/Akt pathway mediates crucial cellular functions regulated by receptor tyrosine kinases, such as cell growth, proliferation, survival and metabolism. Previously, we reported that the whole-body knockout of the Src homology domain-containing adaptor protein Nck1 improves overall glucose homeostasis and insulin-induced activation of the PI3K/Akt pathway in liver of obese mice. The aim of the current study is to elucidate the mechanism by which Nck1 depletion regulates hepatic insulin signaling. RESULTS: Here, we demonstrate that Nck1 regulates the activation of the PI3K/Akt pathway in a protein tyrosine phosphatase 1B (PTP1B)-dependent mechanism. Indeed, depletion of Nck1 by siRNA in HepG2 cells enhances PI3K-dependent basal and growth factor-induced Akt activation. In accordance, primary hepatocytes isolated from Nck1 (-/-) mice also display enhanced Akt activation in response to insulin. Activation of the PI3K/Akt pathway in Nck1-depleted HepG2 cells relies on higher levels of tyrosine-phosphorylated proteins and correlates with decreased PTP1B levels. Interestingly, Nck1 and PTP1B in cells are found in a common molecular complex and their interaction is dependent on the SH3 domains of Nck1. Finally, Nck1 depletion in HepG2 cells neither affects PTP1B gene transcription nor PTP1B protein stability, suggesting that Nck1 modulates PTP1B expression at the translational level. CONCLUSION: Our study provides strong evidence supporting that the adaptor protein Nck1 interacts with PTP1B and also regulates PTP1B expression. In this manner, Nck1 plays a role in regulating the PI3K/Akt pathway.
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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".