Role of MSK1 in the signaling pathway leading to VEGF‐mediated PAF synthesis in endothelial cells
Bibliographic record
Abstract
Vascular endothelial growth factor (VEGF) inflammatory effects require acute platelet-activating factor (PAF) synthesis by endothelial cells (EC). We previously reported that VEGF-mediated PAF synthesis involves the activation of VEGF receptor-2/Neuropilin-1 complex, which is leading to the activation of p38 and p42/44 mitogen-activated protein kinases (MAPKs) and group V secretory phospholipase A(2) (sPLA(2)-V). As the mechanisms regulating sPLA(2)-V remain unknown, we addressed the role of the mitogen- and stress-activated protein kinase-1 (MSK1), which can be rapidly and transiently activated by p38 or p42/44 MAPKs. In native bovine aortic endothelial cells (BAEC), we observed a constitutive protein interaction of MSK1 with p38, p42/44 MAPKs, and sPLA(2)-V. These protein interactions were maintained in BAEC transfected either with the empty vector pCDNA3.1, wild-type MSK1 (MSK1-WT) or N-terminal dead kinase MSK1 mutant (MSK1-D195A). However, in BAEC expressing C-terminal dead kinase MSK1 mutant (MSK1-D565A), the interaction between MSK1 and sPLA(2)-V was reduced by 82% and 90% under basal and VEGF-treated conditions as compared to native BAEC. Treatment with VEGF for 15 min increased basal PAF synthesis in native BAEC, pCDNA3.1, MSK1-WT, and MSK1-D195A by 166%, 139%, 125%, and 82%, respectively. In contrast, PAF synthesis was prevented in cells expressing MSK1-D565A mutant. These results demonstrate the essential role of the C-terminal domain of MSK1 for its constitutive interaction with sPLA(2)-V, which appears essential to support VEGF-mediated PAF synthesis.
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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".