Molecular mechanisms underlying <i>SHP‐1</i> gene expression
Bibliographic record
Abstract
SHP-1, a protein-tyrosine phosphatase with two src-homology 2 domains, is expressed predominantly in hematopoietic and epithelial cells and has been implicated in numerous signaling pathways as a negative regulator. Two promoters direct the expression of human and murine SHP-1, and two types of transcripts (I) and (II) SHP-1, are initiated from each of these promoters. The cDNA sequences of (I)SHP-1 and (II)SHP-1 are identical except in the 5' untranslated region and in the first few coding nucleotides. In this report, we show that promoter usage is similar in mouse and human hematopoietic cells, but different in epithelial cells. In human epithelial cells, only (I)SHP-1 transcripts were expressed. In addition, 4beta-phorbol 12-myristate 13-acetate up-regulates human (I)SHP-1 transcript expression in SKOV3 cells (an ovarian cancer cell line). Indirect evidence suggests that nuclear factor-kappaB might play a role in this induction. We also show that a 12-bp repeat in the distal SHP-1 promoter, which directs (I)SHP-1 expression, is of functional relevance as deletion of one copy of this E-box-containing 12-bp repeat resulted in a significant decrease in promoter activity. Electrophoretic mobility shift assays and supershift experiments showed that the upstream stimulatory factors USF1 and USF2 hetero-dimerize and interact with this 12 bp repeat. Our results suggest that USFs which have antiproliferative functions might regulate the expression of SHP-1, which itself is predominantly a negative growth regulator.
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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) | 0.001 | 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".