RPTPε promotes M2-polarized macrophage migration through ROCK2 signaling and podosome formation
Bibliographic record
Abstract
ABSTRACT Cysteinyl-leukotrienes (cys-LTs) have well-characterized physiopathological roles in the development of inflammatory diseases. We have previously found that protein tyrosine phosphatase ε (PTPε) is a signaling partner of CysLT1R, a high affinity receptor for leukotriene D4 (LTD4). There are two major isoforms of PTPε, receptor-like (RPTPε) and cytoplasmic (cyt-)PTPε, both of which are encoded by the PTPRE gene but from different promoters. In most cells, their expression is mutually exclusive, except in human primary monocytes, which express both isoforms. Here, we show differential PTPε isoform expression patterns between monocytes, M1 and M2 human monocyte-derived macrophages (hMDMs), with the expression of glycosylated forms of RPTPε predominantly in M2-polarized hMDMs. Using PTPε-specific siRNAs and expression of RPTPε and cyt-PTPε, we found that RPTPε is involved in monocyte adhesion and migration of M2-polarized hMDMs in response to LTD4. Altered organization of podosomes and higher phosphorylation of the inhibitory Y-722 residue of ROCK2 was also found in PTPε-siRNA-transfected cells. In conclusion, we show that differentiation and polarization of monocytes into M2-polarized hMDMs modulates the expression of PTPε isoforms and RPTPε is involved in podosome distribution, ROCK2 activation and migration in response to LTD4.
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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 | 0.001 |
| 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".