Fibroblast growth factor receptor 4 (FGFR4) mediates signaling to the prolactin but not the FGFR4 promoter
Bibliographic record
Abstract
Fibroblast growth factor receptors (FGFRs) have been implicated in a multitude of activities. Signaling of the 23 members of the FGF family is mediated through FGFR1-4. We show that FGF-19, which selectively binds FGFR4, can induce prolactin (PRL) but not growth hormone expression. FGF-19 also stimulated MAPK activation, an effect that was abrogated by a soluble dominant negative (dn) form of FGFR4. The response of the pituitary PRL promoter to FGF maps to an Ets-Pit1 binding site. We have previously shown that the hematopoietic zinc finger-containing transcription factor Ikaros (Ik) regulates FGFR4 as part of an overlapping site with that for an Ets-type factor in the FGFR4 promoter. Thus, we examined whether FGF-19 might regulate its own receptor through the Ets-Ik element in the FGFR4 promoter. Ets stimulated and dn-Ets inhibited basal FGFR4 and PRL promoter activity. In contrast, Ets enhanced FGF-19-induced PRL activation but failed to confer an effect for FGF-19 on the FGFR4 promoter. We conclude that FGFR4 mediates FGF-19 signaling to the PRL promoter. Our data also suggest a possible functional role for Ik in sorting Ets signals to the FGFR4 promoter, as distinct from the PRL promoter, where Ets partners with Pit1.
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How this classification was reachedexpand
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 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".