Protein kinase Cθ activity is involved in the 2,3,7,8‐tetrachlorodibenzo‐<i>p</i>‐dioxin‐induced signal transduction pathway leading to apoptosis in L‐MAT, a human lymphoblastic T‐cell line
Bibliographic record
Abstract
The aromatic hydrocarbon receptor (AhR)-dependent pathway involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity has been studied extensively, but the AhR-independent molecular mechanism has not. In previous studies we found that the AhR is not expressed in L-MAT, a human lymphoblastic T-cell line. In this report, we provide the following evidence that the protein kinase C (PKC)theta activity is functionally involved in the AhR-independent signal transduction mechanism that participates in the TCDD-induced L-MAT cell apoptosis. First, only rottlerin, a novel PKC (nPKC)-selective inhibitor, blocked the apoptosis completely, in a dose-dependent manner. Second, PKCtheta was the major nPKC isoform (compared to PKCdelta) expressed in the L-MAT cell line. Third, a cell-permeable myristoylated PKCtheta pseudosubstrate peptide inhibitor also blocked the apoptosis completely, in a dose-dependent manner. Fourth, both rottlerin and myristoylated PKCtheta pseudosubstrate peptide inhibitor completely inhibited PKCtheta kinase activity in vitro at doses that effectively blocked TCDD-induced L-MAT cell apoptosis. TCDD treatment induced a time-dependent activation of nPKC kinase activity in L-MAT cells, and moreover, TCDD induced a translocation of PKCtheta from the cytosolic fraction to the particulate fraction in L-MAT cells. Finally, transient over-expression of a dominant negative PKCtheta (a kinase-dead mutant, K/R 409) in L-MAT cells conferred significant protection against TCDD-induced apoptosis.
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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".