MSK regulate TCR‐induced CREB phosphorylation but not immediate early gene transcription
Bibliographic record
Abstract
Stimulation of the T cell receptor activates the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) cascades. We demonstrate that TCR stimulation also activates the mitogen- and stress-activated kinases (MSK) downstream of ERK1/2 and p38 in both a T cell line and primary peripheral T cells. MSK1/2-knockout mice were found to have normal numbers of T cells in the thymus, and development of these cells appeared unaffected. Using naive T cells and T lymphoblasts from MSK1/2-knockout mice, it was found that MSK was the kinase responsible for phosphorylation of the transcription factor CREB in response to TCR stimulation. Phosphorylation of CREB by MSK has been linked to the transcription of nur77, nor1 and c-fos downstream of MAPK signalling in various cell types. In T cells, the TCR-dependent transcription of these genes was found to require a MAPK-dependent but MSK-independent signalling pathway. Nevertheless, the number of T cells present in the spleens of MSK1/2-knockout mice and the IL-2-induced proliferation of these cells was reduced compared to wild-type mice. This correlated to a reduction in the TCR-induced up-regulation of the IL-2 receptor CD25 and a requirement for MSK in IL-2-induced CREB phosphorylation.
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How this classification was reachedexpand
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) | 0.003 | 0.001 |
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".