Gnaq and Gna11 in the Endothelin Signaling Pathway and Melanoma
Bibliographic record
Abstract
In this article, we first briefly outline the function of G protein coupled receptors in cancer, and then specifically examine the roles of the seven transmembrane G protein coupled Endothelin B receptor (Ednrb) and the G proteins, GNAQ and GNA11, in both melanocyte development and melanoma. Ednrb plays an essential role in melanocyte development. GNAQ and GNA11 are oncogenes when mutated in certain types of melanocytic lesions, being extremely frequent in uveal melanoma, which forms from melanocytes located in the eye. Previously, we reported that in mice, Schwann cell precursor derived melanocytes colonize the dermis and hair follicles, while the inter-follicular epidermis is populated by other melanocytes. A pattern has emerged whereby melanocytes whose activities are affected by gain-of-function mutations of the Endothelin 3 ligand and Gαq/11 are the same subset that arise from Schwann cell precursors. Furthermore, the forced expression of the constitutively active human GNAQ(Q209L) oncogene in mouse melanocytes only causes hyper-proliferation in the subset that arise from Schwann cell precursors. This has led us to hypothesize that in Schwann cell precursor derived melanocytes, Ednrb signals through Gαq/11. Ednrb is promiscuous and may signal through other G protein alpha subunits in melanomas located in the inter-follicular epidermis.
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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 | 0.000 |
| 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 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".