Nck1—an Adaptor Protein Modulating Expression of the Endoplasmic Reticulum (ER) Stress Sensor IRE1α
Bibliographic record
Abstract
The unfolded protein response (UPR) is a cellular mechanism to cope with ER stress induced by alteration in ER homeostasis. Recently, ER stress has been implicated in insulin resistance. In fact, hyperactivation of the IRE1α‐JNK branch of the UPR secondary to obesity has been reported to impair insulin signalling. Interestingly, we identified the adaptor protein Nck1 as an important player in potentiating this UPR signaling pathway in liver. In addition, we observed that depletion of Nck1 resulted in improved hepatic insulin signalling. Therefore, we hypothesized that depletion of Nck1 improved insulin signalling by reducing IRE1α signalling. Testing this hypothesis, we found that basal Akt activation was increased in a PI3K‐dependent manner by depleting Nck1 in HepG2 cells. This correlates with increased levels of tyrosine‐phosphorylated (pY) proteins. Meanwhile, depletion of Nck1 led to reduced IRE1α protein levels and signalling. By blocking Akt activation in Nck1 depleted cells, we further demonstrated that decreased IRE1α expression was independent on Akt activation. Finally, we observed that HepG2 cells depleted of IRE1α also displayed enhanced Akt activation and pY proteins levels. Overall, our data provide strong evidence showing that Nck1 in hepatic cells regulates Akt activation by modulating IRE1α expression and signalling. Supported by Canadian Institutes of Health Research.
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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) | 0.002 | 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".