A requirement of growth factor receptor PTK and metalloproteinase activation in triggering endothelin‐1 (ET‐1)‐induced ERK1/2 and PKB phosphorylation In VSMC.
Bibliographic record
Abstract
A role of growth factor receptor transactivation and metalloproteinase in angiotensin II‐induced signaling events has been well established in vascular smooth muscle cells (VSMC). However, an involvement of receptor transactivation and metalloproteinase activation as upstream mediators of ET‐1‐induced signaling in VSMC has not been explored. In this study, we examined if similar to angiotensin II, ET‐1‐induced ERK1/2, PKB and GSK‐3 phosphorylation also requires transactivation of IGF‐1‐R, EGF‐R and PDGF‐R in VSMC. This possibility was tested by using a series of pharmacological inhibitors. We found that AG1024 and AG1478, inhibitors of IGF‐1‐R, and EGF‐R protein tyrosine kinases (PTKs) respectively, decreased ET‐1‐induced ERK1/2, PKB and GSK‐3 phosphorylation in a dose‐dependent fashion whereas, AG1295 an inhibitor of PDGF‐R‐PTK had no effect on ET‐1‐induced signaling events. Furthermore, PP‐2 a specific inhibitor of Src‐family PTK also blocked ET‐1‐induced phosphorylation of these protein kinases. Doxycycline and GM6001 two specific inhibitors of metalloproteinases, markedly attenuated ET‐1‐induced ERK1/2, PKB and GSK‐3 phosphorylation. These data suggest that, in VSMC, the phosphorylation of ERK1/2, PKB and GSK‐3 induced by ET‐1 is mediated through Src family PTKs, IGF‐1‐R and EGF‐R transactivation as well as metalloproteinase activation and not through PDGF‐R transactivation. (Supported by a grant from CIHR).
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".