Basal and Src kinase‐mediated activation of the EphA2 promoter requires a cAMP‐responsive element but is CREB‐independent
Bibliographic record
Abstract
We have previously identified the EphA2 receptor tyrosine kinase as a potentially important injury-responsive gene and a transcriptional target of Src kinase activity in renal ischemia-reperfusion injury (IRI). In the present study, we confirmed, using EphA2 gene trap mice that the endogenous EphA2 promoter is strongly activated following renal IRI. We also examined in more detail the mechanisms responsible for Src kinase-induced activation of the -2 kb human EphA2 promoter and found that the minimal Src-responsive elements were contained in the -145 to +137 region of the human EphA2 gene. This region contains a canonical cAMP-responsive element (CRE) that we found to be critical for both basal and Src kinase-induced transcriptional activity. However, despite activation of the prototypical CRE-binding factor CREB by the Src kinase Fyn, siRNA-mediated knockdown of CREB had no significant impact on either basal or Fyn-induced EphA2 promoter activity. Similarly, activation of CREB by the adenylate cyclase agonist forskolin failed to induce EphA2 promoter activation. Thus, Src kinase-induced activation of the EphA2 promoter is CRE-dependent but CREB-independent.
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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".