Compartmentation of Cellular cGMP‐signalling: A Mechanism for Spatial and Temporal Regulation of cGMP Mediated Effects
Bibliographic record
Abstract
Cyclic GMP (cGMP) is a ubiquitous intracellular messenger that acts to integrate and translate the information encoded by extracellular messenger molecules including nitric oxide (NO) and natriuretic peptides. Recent evidence suggests that selective activation of the NO‐sensitive guanylyl cyclase results in a localized increase of cGMP which is selectively hydrolyzed by the cGMP specific phosphodiesterase (PDE5). To investigate the role of PDE5 in maintaining this pool of cGMP, we performed selective immunoprecipitations in human platelets and discovered that PDE5 exists in two functional compartments. One compartment is soluble and enzymatically active in resting platelets, while the other fraction exists in a cGMP signaling complex with Protein Kinase G (PKG) and is not active. Interestingly, while the PKG integrated fraction of PDE5 was not activated upon addition of cGMP alone, it was markedly activated upon addition of cGMP and ATP, resulting in PKG dependent phosphorylation of Serine 92. In addition, biochemical fractionation of platelets showed that this PKG complex containing PDE5 was present on the sarcoplasmic reticulum and allows local cGMP‐mediated control of IP 3 ‐stimualted Ca 2+ release. These findings may give insight into the specific effects of nitric oxide and present new targets for sildenafil, a potent PDE5 inhibitor and active ingredient in VIAGRA TM .
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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".