5-Lipoxygenase-activating protein homodimer in human neutrophils: evidence for a role in leukotriene biosynthesis
Bibliographic record
Abstract
FLAP (5-lipoxygenase-activating protein) is a nuclear transmembrane protein involved in the biosynthesis of LTs (leukotrienes) and other 5-LO (5-lipoxygenase) products. However, little is known about its mechanism of action. In the present study, using cross-linkers, we demonstrate that FLAP is present as a monomer and a homodimer in human PMN (polymorphonuclear cells). The functional relevance of the FLAP dimer in LT biosynthesis was assessed in different experimental settings. First, the 5-LO substrate AA (arachidonic acid) concomitantly disrupted the FLAP dimer (at > or =10 microM) and inhibited LT biosynthesis. Secondly, using Sf9 cells expressing active and inactive FLAP mutants and 5-LO, we observed that the FLAP mutants capable of supporting 5-LO product biosynthesis also form the FLAP dimer, whereas inactive FLAP mutants do not. Finally, we showed that FLAP inhibitors such as MK-0591 which block LT biosynthesis in human PMN, disrupt the FLAP dimer in PMN membranes with a similar IC50. The present study demonstrates that LT biosynthesis in intact cells not only requires the presence of FLAP but its further organization into a FLAP homodimer.
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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 | 0.000 | 0.001 |
| 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".