Calcineurin, a serine/threonine phosphatase, is required for GPCR‐triggered association of paxillin, a cytoplasmic adapter protein, with high affinity α4β1 integrins in U937 cells
Bibliographic record
Abstract
The α chain of α4β1 integrins is unique in that it can bind directly to paxillin. Paxillin associates only with high affinity α4β1 that have a dephosphorylated serine‐988 residue in the α4 cytoplasmic tail, which suggests that paxillin regulates leukocyte arrest and migration. On resting U937 cells, α4β1 is predominantly in a low affinity state. Inside‐out signaling through GPCRs induces Ca 2+ ‐calmodulin activation, which is required for up‐regulation of α4β1 affinity. Calmodulin activates calcineurin; hence we investigated whether calcineurin is involved in regulating paxillin association with high affinity α4β1. Using α4 immunoprecipitations, we observed that inhibition of calcineurin with cyclosporin A (CsA) or FK506 (tacrolimus), blocked formyl peptide (FP)‐induced paxillin association in a dose‐dependent manner. However, these inhibitors did not affect FP‐induced α4β1 affinity up‐regulation, determined by soluble ligand binding or FP‐ or SDF‐1α‐triggered U937 cell arrest and accumulation on VCAM‐1‐coated surfaces. Collectively, these data demonstrate that activation of calcineurin is required for the association of paxillin with high affinity α4β1 integrins, but not for affinity modulation or leukocyte arrest. Future studies will focus on the role of paxillin in subsequent steps of emigration, such as leukocyte spreading and transendothelial migration. Supported by CIHR.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".