Requirement of c‐Src in Angiotensin II and Endothelin 1‐induced Activation of MAPKinases in Vascular Smooth Muscle Cells (VSMC)
Bibliographic record
Abstract
Endothelin‐1 (ET‐1) and Angiotensin II (Ang II), two important vasoactive peptides, have been implicated in the pathogenesis of vascular abnormalities such as hypertension and atherosclerosis, through the activation of growth promoting signal transduction pathways, which include mitogen‐activated protein kinases (MAPKs) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB). We have previously shown that c‐Src, a non‐receptor protein tyrosine kinase (NR‐PTK), is an upstream regulator of ET‐1 and Ang II‐induced activation of PKB in VSMC. However, the role of c‐Src in ET‐1‐induced MAPK signaling remains controversial in VSMC. Therefore, in the present studies, we have investigated the involvement of c‐Src in this process. Treatment of VSMC with ET‐1 and Ang II induced phosphorylation of ERK1/2, JNK and p38MAPK in A10 VSMC and in aortic VSMC isolated from 12 week old Wistar Kyoto rats (WK‐VSMC). PP2, an inhibitor of the Src family of NR‐PTK, decreased phosphorylation of ERK1/2, JNK and p38MAPK induced by both ET‐1 and Ang II in a dose‐dependent fashion. Furthermore, knockdown of c‐Src by siRNA also exhibited a similar response, and inhibited ET‐1 and Ang II‐induced ERK1/2, JNK and p38MAPK phosphorylation. In summary, these data suggest that both ET‐1 and Ang II signal the activation of MAPKs through a c‐Src dependent mechanism in VSMC. (Supported by grants from Canadian Institutes of Health Research).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".