Early tyrosine phosphorylation events following adenosine A2A receptor in human neutrophils: identification of regulated pathways
Bibliographic record
Abstract
Abstract Activation of the adenosine 2A receptor (A2AR) elevates intracellular levels of cAMP and acts as a physiologic inhibitor of inflammatory neutrophil functions. In this study, we looked into the impact of A2AR engagement on early phosphorylation events. Neutrophils were stimulated with well-characterized proinflammatory agonists in the absence or presence of an A2AR agonist {3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino] ethyl] phenyl] propanoic acid (CGS 21680)}, PGE2, or a mixture of the compounds RO 20-1724 and forskolin. As assessed by immunoblotting, several proteins were tyrosine phosphorylated; CGS 21680 markedly decreased tyrosine phosphorylation levels of 4 regions (37–45, 50–55, 60, and 70 kDa). Key signaling protein kinases—p38 MAPK, Erk-1/2, PI3K/Akt, Hck, and Syk—showed decreased phosphorylation, whereas Lyn, SHIP-1, or phosphatase and tensin homolog (PTEN) was spared. PGE2 or the intracellular cAMP-elevating combination of RO 20-1724 and forskolin mostly mimicked the effect of CGS 21680. Together, results unveil intracellular signaling pathways targeted by the A2AR, some of which might be key in modulating neutrophil functions.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".