The Proprotein Convertases: Cell Surface and Extracellular Matrix Remodeling
Bibliographic record
Abstract
The family of proprotein convertases (PCs) comprises 9 secretory serine proteinases. The first 7 PCs (PC1, PC2, Furin, PC4, PC5, PACE4 and PC7) cleave secretory substrates at basic residues, while SKI‐1/S1P and PCSK9 cleave at non‐basic residues. Analysis of the phenotypes of knockout (KO) mice allowed the definition of the in vivo roles of the PCs, revealing specific functions in a tissue‐ and time‐dependent manner during development and in adults. PC5 KO mice die at birth and exhibit alterations in multiple organs. Some of these abnormalities were related to the lack of processing of proGDF11, a major regulator of the anterior‐posterior axis during development. However, GDF11‐independent anomalies were also observed in the small intestine, one of the major organs of PC5 expression. Analysis of PC5 substrates in cells revealed that while Furin activates cell surface adhesion molecules such as N‐cadherin, PC5 inactivates it. Furthermore, protein‐C and glypican‐3 (Gpc3) are activated by PC5, Furin and PACE4. Since both N‐cadherin and Gpc3 play major roles in extracellular matrix remodeling during gut development, we analyzed the impact of the lack of PC5 during the development of the gut at embryonic days 10‐18. Amazingly, PC5 KO mice exhibited abnormal looping of the gut, where midgut and dorsal mesentery morphogenesis are clearly impacted. We've identified a similar gut and mesentery phenotype in Wnt5a mutants, as Gpc3 likely facilitates Wnt5a transport or frizzled receptor interaction to direct asymmetric midgut development. Analysis of the gut of PC5 KO mice revealed the lack of protein expression of Gpc3, suggesting that PC5 is needed to either stabilize the protein or prevent its degradation. Our data show that PC5 regulates gut development by remodeling the extracellular matrix.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".