Protein tyrosine phosphatase 1B regulates metabolic, oncogenic, and hematopoietic function
Bibliographic record
Abstract
Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed enzyme that is involved in multiple signaling pathways. Biochemical and substrate trapping studies have implicated PTP1B in the dephosphorylation of various tyrosine kinases, including the EGFR, PDGFR, IR, IGF-IR, JAK2, p210Bcr-Abl, and Src. Of particular interest, gene-targeting studies in mice have established PTP1B as a critical physiological regulator of metabolism by attenuating insulin and leptin signaling. Indeed, PTP1B null mice exhibit resistance to diet-induced diabetes and obesity. Although PTP1B is involved in signaling pathways that contribute to oncogenesis, PTP1B null mice do not develop spontaneous tumors. Therefore, my doctoral research focuses on identifying the physiological significance of PTP1B in these pathways. Our laboratory has previously demonstrated that PTP1B modulates leptin signaling via the tyrosine kinase JAK2. Accordingly, I have shown that PTP1B dephosphorylates JAK2 in a growth hormone (GH)-dependent manner, thus negatively regulating GH signaling and downstream effectors such as STAT3 and STAT5. Consequently, mice lacking PTP1B remain sensitive to GH action after starvation. In addition, I showed that the absence of PTP1B could improve glycemia during streptozotocin-induced type 1 diabetes. In the second part of my research, I have elucidated the mechanism for the previously reported decreased ERK activation in PTP1B null fibroblasts. I demonstrated that Ras activity is reduced in these cells, which is due to increased p120RasGAP expression and p62Dok hyperphosphorylation. Both of these molecules negatively regulate Ras activity by promoting the intrinsic GTPase activity of Ras, leading to decreased ERK activation. Finally, I developed a mouse model of cancer to study the role of PTP1B in tumorigenesis. Since the majority of cancers harbor mutations in p53, I generated p53/PTP1B double null mice. In the absence of p53, PTP1B heterozygous
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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 | 0.000 |
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 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".