A Polyaromatic Caveolin-Binding-Like Motif in the Cytoplasmic Tail of the Type 1 Receptor for Angiotensin II Plays an Important Role in Receptor Trafficking and Signaling
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Bibliographic record
Abstract
The type 1 receptor for angiotensin II (AT(1)) is a member of the G protein-coupled receptor family. The presence of a caveolin-binding-like motif (phiXphiXXXXphiXXphi where phi is an aromatic residue) within the cytoplasmic tail of the AT(1) receptor suggests an implication for caveolae in the functionality of this receptor. We constructed a mutant AT(1) receptor where each of the aromatic residues in the caveolin-binding-like motif were replaced by alanine (AT(1)-YFFY/A). Mutation of this motif considerably reduced the plasma membrane expression of the receptor that accumulated in a perinuclear compartment. The agonist-induced internalization rate of the AT(1)-YFFY/A receptor was also significantly reduced. Finally, the AT(1)-YFFY/A receptor was poorly activated as indicated by a low agonist-induced production of inositol phosphates. Unexpectedly, the proportion of AT(1) receptor found in caveolae was minor under basal conditions and did not increase under stimulated conditions. Coexpression of the AT(1) receptor with dopamine receptor interacting protein of 78 kDa, a protein implicated in the cellular routing of the dopamine D1 receptor, increased plasma membrane expression of the AT(1) receptor. However, dopamine receptor interacting protein of 78 kDa had no effect on the expression of the AT(1)-YFFY/A receptor. Taken together, these results suggest that the caveolin-binding-like motif of the AT(1) receptor does not promote localization of the receptor to caveolae but rather may act as a docking site for regulatory proteins modulating the routing and the functionality of the receptor.
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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 | 0.000 | 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) | 0.000 | 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 it