Role of protein kinase D (PKD) phosphorylation of Oxysterol binding protein (OSBP) in sphingomyelin biosynthesis
Bibliographic record
Abstract
Oxysterol binding protein (OSBP) is a high affinity receptor for oxysterols that interacts with the endoplasmic reticulum (ER) and trans‐Golgi network via FFAT and pleckstrin homology (PH) domains, respectively. In vitro, OSBP displays cholesterol extraction and transfer activity and regulates the cholesterol content of Golgi and post‐Golgi membranes. Through this activity, OSBP controls CERT‐mediated ER‐to‐Golgi ceramide transfer, which is the rate‐determining step in sphingomyelin (SM) biosynthesis. CERT and OSBP are phosphorylated by protein kinase D (PKD), thus we investigated whether CERT activity and SM synthesis is regulated by OSBP phosphorylation at serine 242 by PKD. OSBP and PKD are physically associated, however OSBP is not required for Golgi association and activation of PKD. While transfection of wild‐type OSBP restored sterol activation of SM biosynthesis in OSBP‐depleted CHO cells, OSBP S242A and S242D were ineffective. Another OSBP‐related protein ORP9, which transfers cholesterol from ER to Golgi but is not involved in SM biosynthesis, is not a substrate for or associated with PKD. We conclude that an OSBP phosphorylation/dephosphorylation cycle mediated by PKD is necessary and specific for OSBP function in the context of regulating SM biosynthesis. Supported by the Canadian Institutes of Health Research.
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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 | 0.001 |
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".