Human adenylyl cyclase 9 is auto-stimulated by its isoform-specific C-terminal domain
Bibliographic record
Abstract
Human transmembrane adenylyl cyclase 9 (AC9) is not regulated by heterotrimeric G proteins. Key to the resistance to stimulation by Gs-coupled receptors (GsRs) is auto-inhibition by the COOH-terminal domain (C2b). The present study investigated the role of the C2b domain in the regulation of cyclic AMP production by AC9 in HEK293FT cells expressing the GloSensor22F cyclic AMP-reporter protein. Surprisingly, we found C2b to be essential for sustaining the basal output of cyclic AMP by AC9. A human mutation (E326D) in the parallel coiled-coil formed by the signalling helices of AC9 dramatically increased basal activity, which was also dependent on the C2b domain. Intriguingly, the same mutation enabled stimulation of AC9 by GsRs. In summary, auto-regulation by the C2b domain of AC9 sustains its basal activity and quenches activation by GsR. Thus, AC9 appears to be tailored to support constitutive activation of cyclic AMP effector systems. A switch from this paradigm to stimulation by GsRs may be occasioned by conformational changes at the coiled-coil or removal of the C2b domain.
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 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 | 0.000 |
| 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".