A Role for Phosphatidylinositol 3-Kinase in TCR-Stimulated ERK Activation Leading to Paxillin Phosphorylation and CTL Degranulation
Bibliographic record
Abstract
PI3K is an important regulator of a number of cellular processes. We examined the contribution of PI3K to mouse CTL signaling, leading to degranulation. We show that TCR-triggered, but not phorbol ester and calcium ionophore-induced, CTL degranulation is dependent on PI3K activity. Although PI3K activity is required for optimal LFA-1-mediated adhesion and cell spreading, this most likely does not account for its full contribution to degranulation. We demonstrate that PI3K is required for TCR-stimulated ERK activation in CTL, which we have shown previously to be required for CTL degranulation. We thus define a pathway through which PI3K most likely regulates degranulation and in which ERK appears to be a key signaling molecule. Furthermore, we identified the cytoskeletal adaptor paxillin as a target of ERK downstream of TCR stimulation. Consistent with a role in degranulation, we demonstrate that paxillin is localized to the microtubule organizing center in resting cells and upon target cell binding is recruited to the contact point with the target cell. These studies demonstrate that PI3K regulates ERK activity leading to CTL degranulation, and identify paxillin as a target of ERK downstream of the TCR. That paxillin is independently phosphorylated by both tyrosine kinase(s) and ERK downstream of the TCR and localized both at the microtubule organizing center and at the target cell contact point suggests an important role for paxillin in CTL-mediated killing.
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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 | 0.000 |
| 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".