Integrin activation results in cSrc mediated phosphorylation and potentiation of Maxi K channels
Bibliographic record
Abstract
The goal of this study was to determine the mechanism by which α5β1 integrin activation enhances current through the large conductance, calcium‐sensitive K + channel (BK). Excised, inside‐out patch clamp methods were used to record macroscopic BK currents in HEK 293 cells transiently expressing the BK pore‐forming α subunit (m Slo ). Channel activity was acutely enhanced following α5β1 integrin activation by application of soluble α5β1 integrin antibody to the outside of the patch. The amplitude of current was increased; G‐V relations were left‐shifted at free [Ca 2+ ] from 1 to 100 μM; the speed of channel activation was increased at 0 [Ca 2+ ]. Over‐expression of active c Src , but not catalytically dead c Src , with m Slo led to comparable enhancement of BK channel activity at any given free [Ca 2+ ]. Expression of dead c Src or acute application of the c Src inhibitor, PP2, in the presence of endogenously expressed c Src blocked the enhancement of BK current by integrin activation. Currents from mutant m Slo containing a single tyrosine mutation at Y766F failed to show Ca 2+ sensitivity changes following c Src over‐ expression or integrin activation. However, shifts in Ca 2+ sensitivity remained in mutants with tyrosine substitutions at Y935F and Y1027F. We conclude that BK channel activity is potentiated by α5β1 integrin activation via c‐ Src ‐mediated phosphorylation of the channel C‐terminus at residue Tyr766. Supported by NIH, HL‐71796
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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".