GPCR activation of CFTR through two independent phosphorylation pathways
Bibliographic record
Abstract
Cystic Fibrosis Transmembrane conductance Regulator (CFTR) activation by PKA and PKC has been extensively studied, however its regulation by receptors is less well understood. To study signaling upstream of the kinases, we measured whole‐cell Cl‐currents in BHK cells cotransfected with GPCRs and CFTR. In cells expressing the M3 muscarinic acetylcholine receptor, the agonist carbachol (Cch) caused strong activation of CFTR through two pathways; the canonical PKA‐dependent mechanism and a second mechanism mechanism that involves tyrosine phosphorylation. The role of PKA was suggested by partial activation of a mutant lacking tyrosine residues that mediate stimulation by the tyrosine kinase c‐Src. The role of tyrosine kinases was suggested by the ability of Cch to stimulate 15SA CFTR, a mutant which lacks 15 potential PKA sites and is unresponsive to PKA stimulation, and also by the sensitivity of the Cch response to inhibitors of the tyrosine kinase c‐Src. The results suggest that CFTR phosphorylation by PKA and tyrosine kinases both contribute to CFTR regulation by GPCRs that are expressed at the apical membrane of intestinal and airway epithelia. Supported by GEPROM, GRASP, the McGill (CIHR) Chemical Biology program, and the Canadian Foundation for Innovation.
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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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".