Conformational sampling of membranes by Akt controls its activation and inactivation
Bibliographic record
Abstract
Significance Akt is a paradigmatic lipid-activated kinase, which is frequently hyperactivated in human cancer. In the absence of PI(3,4,5)P 3 or PI(3,4)P 2 , Akt is maintained in an inactive conformation by an inhibitory interaction between its membrane-binding PH domain and its kinase domain. Here, we describe the conformational changes associated with its binding to PI(3,4,5)P 3 , leading to disruption of the inhibitory PH−kinase interface, and its consequent activation by protein kinases. Intriguingly, we find that reversal of those conformational changes promotes its inactivation by protein phosphatases. The activation of Akt is thereby restricted to discrete membrane locations, and it is rapidly inactivated upon dissociation. We propose a model in which activation, substrate phosphorylation, and inactivation of Akt are tightly coupled to the membrane.
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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 | 0.000 |
| 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".