Interaction of p38 and Sp1 in a Mechanical Force-induced, β1 Integrin-mediated Transcriptional Circuit That Regulates the Actin-binding Protein Filamin-A
Bibliographic record
Abstract
Connective tissue cells in mechanically active environments survive applied physical forces by modifying actin cytoskeletal structures that stabilize cell membranes. In fibroblasts, tensile forces induce the expression of filamin-A, a mechanoprotective actin-binding protein, but the mechanisms and protein interactions by which force activates filamin-A transcription are not defined. We found that in fibroblasts, application of tensile forces through collagen-coated magnetite beads to cell surface beta(1) integrins induced filamin-A expression. This induction required actin filaments and selective activation of the p38 mitogen-activated protein kinase. Force promoted the redistribution of p38 to the integrin/bead locus and the nucleus as well as enhanced binding of the transcription factor Sp1 to proximal, regulatory domains of the filamin-A promoter. Force application increased association of Sp1 with p38 and phosphorylation of Sp1. Transcriptional activation of filamin-A in force-treated fibroblasts was subsequently mediated by Sp1-binding sites on the filamin-A promoter. These results provide evidence for a mechanically coupled transcriptional circuit that originates at the magnetite bead/integrin locus, activates p38, tethers p38 to actin filaments, promotes binding of p38 to Sp1 in the nucleus, and induces filamin-A expression.
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 | 0.000 | 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".