Role of ßarrestin in the B2R‐mediated ERK activation
Bibliographic record
Abstract
ßarrestins are multifunctional adaptors that regulate the clathrin‐dependent internalization and signalling of G protein‐coupled receptors (GPCRs). We have previously reported that the bradykinin B2 receptor (B2R) forms a stable complex with ßarrestin in endosomes and recycles rapidly to the plasma membrane albeit its high avidity to ßarrestin. Several reports indicate that ßarrestins play a role in the ERK activation through G protein‐independent mechanisms. The present study aims at determining the role of ßarrestin in the B2R‐mediated ERK activation. We first used a B2R mutant which exhibit an increased avidity for ßarrestin and examined the kinetics of ERK activation by western Blot. This mutant showed a higher ERK activation compared to the wild‐type receptor. We also tested the effect of the ßarrestin2‐381T mutant, which has an increased avidity for B2R, and showed that it increased ERK activation mediated by bradykinin. In mouse embryonic fibroblasts (MEF) from βarrestin knockout mice, activation of the endogenous B2R led to a transient ERK activation. Introduction of ßarrestin to the MEF cells led to a sustained ERK activation. Finally using immunoprecipitaion assay we showed that ERK is recruited to the B2R/ßarrestin complex. These experiments show the involvement of ßarrestin in the activation of the ERKs through the B2R.
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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".