ORP9 negatively regulates phosphorylation of serine 473 in Akt
Bibliographic record
Abstract
Oxysterol binding protein‐related protein 9 (ORP9) is a member of the ORP gene family implicated in ER/Golgi transport and lipid regulation. Due to alternate promoter start sites, ORP9 exists as a long (ORP9L) and an N‐terminal truncated short form (ORP9S). An antibody that recognizes phospho‐S473 in the hydrophobic‐motif of Akt was found to cross‐react with ORP9. Similar to Akt and other AGC kinases, PDK‐2 potentially phosphorylates ORP9 at a related motif on S287. RNAi and inducibly overexpressing CHO cells were used to identify the ORP9 S287 kinase, and assess the role of ORP9 in Akt regulation. Initial experiments using 32 P labeling, in vitro phosphatase assays and mutagenesis confirmed that ORP9 S287 was phosphorylated. Treatment of CHO cells with LY294002 resulted in decreased ORP9 phosphorylation suggesting involvement of the PI‐3 kinase pathway. However, TPAβ increased ORP9 S287 phosphorylation and co‐immunoprecipation assays revealed an interaction between ORP9 and PKCβII, indicating that PKCβII is the ORP9 S287 kinase. RNAi of ORP9L in HEK 293 cells increased Akt phospho‐S473 4‐fold whereas Akt phospho‐T308 was unaffected, implying that ORP9 is a negative regulator of Akt activity. In addition, enforced overexpression of ORP9S, but not ORP9L, in CHO cells inhibited proliferation. This may reflect inhibition of Akt phosphorylation at S473 and subsequent activation of downstream targets involved in cell proliferation. We propose that ORP9 negatively regulates the PI‐3 kinase/Akt pathway by altering phospho‐S473 through interaction with PKCβII, a potential PDK‐2.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".