Proadrenomedullin N-Terminal 20 Peptides (PAMPs) Are Agonists of the Chemokine Scavenger Receptor ACKR3/CXCR7
Bibliographic record
Abstract
Abstract Adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two peptides with vasodilative, bronchodilative, and angiogenic properties, originating from a common precursor, proADM. Previous studies proposed that the atypical chemokine receptor ACKR3 might act as a low-affinity scavenger for ADM, regulating its availability for its cognate receptor calcitonin receptor-like receptor (CLR) in complex with a receptor activity modifying protein (RAMP). In this study, we compared the activation of ACKR3 by ADM and PAMP, as well as other related members of the calcitonin gene-related peptide (CGRP) family. Irrespective of the presence of RAMPs, ADM was the only member of the CGRP family to show moderate activity toward ACKR3. Remarkably, PAMP, and especially further processed PAMP-12, had a stronger potency toward ACKR3 than ADM. Importantly, PAMP-12 induced β-arrestin recruitment and was efficiently internalized by ACKR3 without inducing G protein or ERK signaling in vitro. Our results further extend the panel of endogenous ACKR3 ligands and broaden ACKR3 functions to a regulator of PAMP-12 availability for its primary receptor Mas-related G-protein-coupled receptor member X2 (MrgX2).
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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) | 0.003 | 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".