Signaling through CD16b in human neutrophils involves the Tec family of tyrosine kinases
Bibliographic record
Abstract
Tec kinases belong to the second largest family of nonreceptor tyrosine kinases. Although these kinases are expressed in myeloid cells, little is known about their implication in neutrophil function. We recently reported the participation of Tec kinases in the responses of human neutrophils to the bacterial peptide N-formyl-l-methionyl-l-leucyl-l-phenylalanine via G-coupled protein receptors. In this study, we extended our investigations of Tec kinases to the signaling of the glycosylphosphatidylinositol-linked receptor CD16b, which is highly and specifically expressed in neutrophils. The results obtained indicate that Tec is translocated to the plasma membrane, phosphorylated, and activated upon CD16b cross-linking and that the activation of Tec is inhibited by Src-specific inhibitors as well as by the phosphatidylinositol-3 kinase inhibitor, wortmannin. As no specific inhibitor of Tec exists, the role of Tec kinases was further investigated using a-Cyano-b-hydroxy-b-methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13), a compound known to inhibit Bruton's tyrosine kinase. We show that this compound also inhibits the kinase activity of Tec and provide evidence that the mobilization of intracellular calcium and the tyrosine phosphorylation of phospholipase Cgamma2 (PLCgamma2) induced upon CD16b engagement are inhibited by LFM-A13. We also show that Tec kinases are important for CD16b-dependent degranulation of neutrophils. In summary, we provide direct evidence for the implication of Tec in CD16b signaling and suggest that Tec kinases are involved in the phosphorylation and activation of PLCgamma2 and subsequently, in the mobilization of calcium in human neutrophils.
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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 | 0.000 | 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".