Regulation of Angiopoietin‐1/Tie‐2 Receptor Signaling in Endothelial Cells by Dual‐Specificity Phosphatases 1, 4, and 5
Bibliographic record
Abstract
BACKGROUND: Angiopoietin-1 (Ang-1) promotes survival and migration of endothelial cells, in part through the activation of mitogen-activated protein kinase (MAPK) pathways downstream of Tie-2 receptors. Dual-specificity phosphatases (DUSPs) dephosphorylate phosphotyrosine and phosphoserine/phosphothreonine residues on target MAPKs. The mechanisms by which DUSPs modulate MAPK activation in Ang-1/Tie-2 receptor signaling are unknown in endothelial cells. METHODS AND RESULTS: Expression of various DUSPs in human umbilical vein endothelial cells exposed to Ang-1 was measured. The functional roles of DUSPs in Ang-1-induced regulation of MAPK activation, endothelial cell survival, migration, differentiation, and permeability were measured using selective siRNA oligos. Ang-1 differentially induces DUSP1, DUSP4, and DUSP5 in human umbilical vein endothelial cells through activation of the PI-3 kinase, ERK1/2, p38, and SAPK/JNK pathways. Lack-of-function siRNA screening revealed that DUSP1 preferentially dephosphorylates p38 protein and is involved in Ang-1-induced cell migration and differentiation. DUSP4 preferentially dephosphorylates ERK1/2, p38, and SAPK/JNK proteins and, under conditions of serum deprivation, is involved in Ang-1-induced cell migration, several antiapoptotic effects, and differentiation. DUSP5 preferentially dephosphorylates ERK1/2 proteins and is involved in cell survival and inhibition of permeability. CONCLUSIONS: DUSP1, DUSP4, and DUSP5 differentially modulate MAPK signaling pathways downstream of Tie-2 receptors, thus highlighting the importance of these phosphatases to Ang-1-induced angiogenesis.
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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 | 0.000 | 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) | 0.000 | 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".