Proteolytic processing of a human salivary proline‐rich protein precursor by proprotein convertases
Bibliographic record
Abstract
Salivary proline-rich proteins (PRPs) are synthesized as precursors that are cleaved before secretion giving rise to glycosylated PRPs which have lubricating function and basic PRPs which are potent precipitators of dietary tannins. The putative cleavage sites in the precursors for basic and glycosylated PRPs all conform to the sequence RSXR downward arrowS (X can be A, S or P) in agreement with the recognition sequence (RXXR downward arrow) for various proprotein convertases. PRB4S, a proprotein giving rise to a basic PRP (IB-5) as well as a glycosylated PRP (II-1) was synthesized by in vitro transcription-translation. It was cleaved by furin at RSAR downward arrowS(173-178) giving rise to two proteins II-1 and IB-5. Similarly another precursor with the sequence RSAR downward arrowS(173-178) was also cleaved by furin. This together with previous results show that in vitro furin can cleave all RSXR downward arrowS sequences in the proproteins that give rise to glycosylated and basic PRPs. To demonstrate cellular cleavage, a human submandibular cell line (HSG) was transfected with a vector encoding PRB4S. This resulted in secretion of II-1 and IB-5. The degree of cleavage was enhanced by coexpressing furin and PRB4S. No cleavage occurred if the cells expressed a mutant PRB4S, R177Q, where the furin cleavage site had been destroyed. Cleavage was also inhibited if a furin inhibitor was coexpressed with PRB4S. Incubating the cells at 20 degrees C which blocks exit of proteins from the trans-Golgi network demonstrated that cleavage occurs before exit of the proteins from this network. These results show that furin may be responsible for in vivo cleavage of PRP precursors. Transfecting furin-deficient RPE.40 cells with a vector encoding PRB4S also led to secretion of II-1 and IB-5 showing that convertases other than furin can also cleave PRB4S in tissue culture.
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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 | 0.001 | 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".