Differential stimulation of c-Kit mutants by membrane-bound and soluble Steel Factor correlates with leukemic potential
Bibliographic record
Abstract
The authors investigated the roles of PI3-kinase and PLC-gamma in stimulation by Steel Factor (SLF) through c-Kit. c-Kit mutants YF719, YF728, and a YF719/YF728 double mutant were expressed in 32D myelomonocytic cells. KitYF719 fails to recruit PI3-kinase after stimulation with SLF, whereas KitYF728 fails to stimulate PLC-gamma phosphorylation or mobilize Ca(++). Both single mutants responded mitogenically to soluble SLF (sSLF) in a manner indistinguishable from wild type (WT), although sSLF failed to stimulate or promote the survival of cells expressing the double mutant. In contrast, although cells expressing WT or YF719 were mitogenically stimulated by membrane-bound SLF (mSLF), stimulation of cells expressing KitYF728 was impaired. Similarly, cells expressing WT or YF719 receptors were stimulated by plate-bound anti-Kit antibodies, whereas cells expressing the YF728 receptor were not stimulated. Neomycin sulfate, a PLC antagonist, inhibited cells expressing YF719 receptors stimulated by sSLF. Neomycin also inhibited cells expressing the WT receptor that were stimulated by mSLF or immobilized anti-Kit antibodies but did not inhibit stimulation of cells expressing WT or YF719 receptors by sSLF. 32D cells expressing KitWT, KitYF719, or KitYF728 were injected into mice and the presence of cells was evaluated by colony assays 6 to 7 weeks later. Although both KitWT and KitYF719 expressing cells could be recovered from the spleen and bone marrow, recovery of KitYF728 cells from these organs was severely reduced. These results indicate that Kit tyrosine 728 is of particular importance for mitogenic stimulation by mSLF or immobilized ligand and is required for full maintenance of cells in vivo, likely through activation of PLC-gamma. (Blood. 2000;96:3734-3742)
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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) | 0.006 | 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".