CD63 Modulates Spreading and Tyrosine Phosphorylation of Platelets on Immobilized Fibrinogen.
Bibliographic record
Abstract
Abstract CD63 is a member of the tetraspanin superfamily of integral membrane proteins. Present on a variety of cells, tetraspanins form lateral associations with integrins and may act as ‘organizers’ of multimolecular networks that modulate integrin-mediated signaling, cell morphology, motility and migration. In resting platelets CD63 is present on the membranes of dense granules and lysosomes. Following platelet activation and exocytosis, CD63 relocates to the plasma membrane where it associates with the platelet integrin αIIbβ3-CD9 complex, and with the actin cytoskeleton in an αIIbβ3-dependent manner. In the current study, D545, a monoclonal antibody directed at the second extracellular loop of CD63, was used to investigate the role of CD63 in platelet adhesion, spreading and tyrosine phosphorylation, as determined by immunofluorescence microscopy, confocal imaging and immunoblotting. As previously demonstrated, D545 did not alter adhesion of platelets to fibrinogen, but did affect platelet spreading. Thrombin-activated platelets showed marked spreading, F-actin reorganization, redistribution of vinculin and extensive tyrosine phosphorylation, all of which were inhibited by D545. Similarly D545 inhibited the phosphorylation of focal adhesion kinase in thrombin-activated adherent platelets. These results suggest that CD63 may modulate αIIbβ3-dependent cytoskeletal reorganization. In some malignant cell lines CD63 has been shown to associate with phosphatidylinositol (PI) kinase. To address a similar association in platelets, lipid kinase assays were performed on D545 immunoprecipitates, using PI as substrate. CD63 co-immunoprecipitated with a lipid kinase that was stimulated by non-ionic detergents, inhibited by adenosine, but unaffected by wortmannin. These enzymatic properties are consistent with a PI 4-kinase type II. The CD63-PI 4-kinase complex was co-purified from both resting and activated platelets and therefore was not activation-dependent. The linkage of CD63 with PI 4-kinase may result in the recruitment of the signaling enzyme to specific membrane locations and influence phosphoinositide-dependent signaling.
Stored with the screening record, where it is evidence for the labels above.
How this classification was reachedexpand
The three-model screen
all 5,600 screened works →All three models called this out of scope.
Cell biology of CD63 in platelet spreading and tyrosine phosphorylation; the object is a molecular mechanism.
This biomedical experiment studies platelet signaling and CD63 function, not research practice.
Platelet biology experiment on CD63 and integrin signaling; biomedical domain.
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".