PERK phosphorylation on tyrosine 561 delays ER stress‐induced PERK activation
Bibliographic record
Abstract
The PKR‐like endoplasmic reticulum (ER) kinase (PERK) is an ER transmembrane ser/thr protein kinase that plays an essential role in mediating the unfolded protein response (UPR) activated during stress conditions in the ER lumen. The importance of PERK in pancreatic beta‐cell homeostasis is demonstrated in Wolcott‐ Rallison syndrome, a neonatal or early infancy form of insulin‐dependent diabetes in humans with inactivating mutations in the PERK gene. In this study, we provide strong evidence that PERK is phosphorylated on tyrosine 561 (Y561) in pervanadate‐treated MIN6 cells, a mouse pancreatic beta cell line in culture. In addition, we demonstrate that increased phosphorylation of PERK on Y561 delays PERK activation in response to pharmacological agents that induce ER stress. Interestingly, we discovered that the adaptor protein Nck1 directly interacts with PERK phosphorylated on Y561 through its SH2 domain. Finally, using recombinant wild‐type and kinase dead PERK proteins, our data strongly suggest that PERK phosphorylation on Y561 is dependent on PERK kinase activity. All together, our results indicate that PERK phosphorylation on Y561 and binding to Nck1 play an important role in regulating PERK activity. Supported by the Canadian Diabetes Association.
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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 | 0.000 |
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, 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".