Divers Modalities Of Β-Arrestin2 Recruitment To CXCR4, Independently Of G-Protein Activation
Bibliographic record
Abstract
Poster presented on May 31st, 2013, at the 18th annual symposium of Immuno-Inflamation, Eastman, QC, Canada. ABSTRACT CXCR4, a chemokine receptor involved in metastasis, signals through two major successive pathways: Gα/i and β-arrestin. β-arrestin terminates G-protein signaling and targets the receptor to endocytosis. Constitutively active GPCR mutants (CAMs) spontaneously activate G-protein. Constitutively inactive mutants (CIMs) that spontaneously recruit β-arrestin are devoid of G-protein signaling. We tested a set of CXCR4 mutants on their signaling capacity of Gα/i and ß-Arrestin2 pathways. R134A was found a CIM that was inactive on the Gα/i signaling, but constitutively recruited arrestin. N119S was found as a CAM, constitutively active in G-protein signaling as well as β-arrestin recruitment. Imaging of these two mutants showed their constitutive internalization and their different localization in the cell. These results show the presence of varying β-arrestin recruitment, independent of the G-protein signaling. Further studies remain to conclude whether the difference of β-arrestin recruitment is directed by the GRKs or the ubiquitination of the receptor.
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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) | 0.008 | 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".