Together and apart: inhibition of DNA synthesis by connexin-43 and its relationship to transforming growth factor β
Bibliographic record
Abstract
The membrane and channel protein connexin-43 (Cx43), as well as the cytokine transforming growth factor (TGF) β, suppress proliferative growth in cardiomyocytes and other cell types. Previously we showed that the inhibitory effect of Cx43 is canceled when Cx43 becomes phosphorylated at serine (S) 262 in response to mitogen stimulation. We have now asked if the TGFβ-triggered inhibition of DNA synthesis is associated with changes in Cx43 phosphorylation at S262. Conversely, we investigated if inhibition of DNA synthesis by overexpressed Cx43 is dependent on engaging TGFβ signal transduction. We report that TGFβ acutely prevented mitogen-induced Cx43 phosphorylation at S262, while chronic inhibition of TGFβ signal transduction raised baseline levels of endogenous phospho-S262-Cx43 without affecting total Cx43. Inhibition of baseline TGFβ signal transduction through (a) inhibiting TGFβ receptor I (TGFβRI) with SB431542, (b) inhibiting TGFβ receptor II (TGFβRII) by overexpressing dominant-negative (DN) TGFβRII, (c) inhibiting the downstream signaling mediator Smad2 by overexpressing DN Smad2, each separately increased baseline cardiomyocyte DNA synthesis, but could not reverse DNA synthesis inhibition by overexpressed Cx43. It is suggested that inhibition of cardiomyocyte DNA synthesis by TGFβ/TGFβRI/II/phospho-Smad2 signaling is mediated, at least in part, by reducing endogenous phospho-S262-Cx43 levels.
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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) | 0.002 | 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".