Protein Tyrosine Phosphatase-1B Dephosphorylation of the Insulin Receptor Occurs in a Perinuclear Endosome Compartment in Human Embryonic Kidney 293 Cells
Bibliographic record
Abstract
Protein tyrosine phosphatase-1B (PTP-1B) is a negative regulator of insulin signaling. It is thought to carry out this role by interacting with and dephosphorylating the activated insulin receptor (IR). However, little is known regarding the nature of the cellular interaction between these proteins, especially because the IR is localized to the plasma membrane and PTP-1B to the endoplasmic reticulum. Using confocal microscopy and fluorescence resonance energy transfer (FRET), the interaction between PTP-1B and the IR was examined in co-transfected human embryonic kidney 293 cells. Biological activities were not significantly affected for either PTP-1B or the IR with the fusion of W1B-green fluorescent protein (GFP) to the N terminus of PTP-1B (W1B-PTP-1B) or the fusion of Topaz-GFP to the C terminus of the IR (Topaz-IR). FRET between W1B and Topaz was monitored in cells transfected with either wild type PTP-1B (W1B-PTP-1B) or the substrate-trapping form PTP-1B(D181A) (W1B-PTP-1B(D181A)) and Topaz-IR. Co-expression of W1B-PTP-1B with Topaz-IR resulted in distribution of Topaz-IR to the plasma membrane, but no FRET was obtained upon insulin treatment. In contrast, co-expression of W1B-PTP-1B(D181A) with Topaz-IR caused an increase in cytosolic Topaz-IR fluorescence and, in some cells, a significant basal FRET signal, suggesting that PTP-1B is interacting with the IR during its synthesis. Stimulation of these cells with insulin resulted in a rapid induction of FRET that increased over time and was localized to a perinuclear spot. Co-expression of Topaz-IR with a GFP-labeled RhoB endosomal marker and treatment of the cells with insulin identified a perinuclear endosome compartment as the site of localization. Furthermore, the insulin-induced FRET could be prevented by the treatment of the cells with a specific PTP-1B inhibitor. These results suggest that PTP-1B appears not only to interact with and dephosphorylate the insulin-stimulated IR in a perinuclear endosome compartment but is also involved in maintaining the IR in a dephosphorylated state during its biosynthesis.
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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) | 0.001 | 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 | 0.002 |
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".