Protein-tyrosine Phosphatase MEG2 Is Expressed by Human Neutrophils
Bibliographic record
Abstract
Signaling pathways involving reversible tyrosine phosphorylation are essential for neutrophil antimicrobial responses. Using reverse transcriptase PCR, expression of the protein-tyrosine phosphatase MEG2 by peripheral neutrophilic polymorphonuclear leukocytes (PMN) was identified. Polyclonal antibodies against MEG2 were developed that confirmed expression of MEG2 protein by PMN. Through a combination of immunofluorescence and cell fractionation followed by immunoblotting, we determined that MEG2 is predominantly cytosolic with components present in secondary and tertiary granules and secretory vesicles. MEG2 activity, as determined by immunoprecipitation and in vitro phosphatase assays, is inhibited after exposure of cells to the particulate stimulant opsonized zymosan or to phorbol 12-myristate 13-acetate but largely unaffected by the chemoattractant N-formyl-methionyl-leucyl-phenyalanine. Studies using bacterially expressed glutathione S-transferase MEG2 fusion protein indicate that cysteine 515 is essential for catalytic activity, whereas the noncatalytic (N-terminal) domain of MEG2 negatively regulates the enzymatic activity of the C-terminal phosphatase domain. The activity of MEG2 is enhanced by specific polyphosphoinositides with the order of potency being phosphatidylinositol (PI) 4,5-diphosphate > PI 3,4,5-triphosphate > PI 4-phosphate. MEG2 associates at an early stage with nascent phagosomes. Taken together, our results indicate that MEG2 is a polyphosphoinositide-activated tyrosine phosphatase that may be involved in signaling events regulating phagocytosis, an essential antimicrobial function in the innate immune response.
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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 | 0.000 |
| 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".