The antitumor ether lipid 1-Q-octadecyl-2-O-methyl-rac-glycerophosphocholine (ET-18-OCH3) inhibits the association between Ras and Raf-1.
Bibliographic record
Abstract
BACKGROUND: Previous studies have shown that the antitumor ether lipid, 1-O-Octadecyl-2-O-methyl-rac-glycerophosphocholine (ET-18-OCH3), inhibits the activation of the MAPK pathway in EGF- and serum-stimulated MCF-7 cells. The activation of the MAPK pathway subsequent to growth factor stimulation requires the recruitment of Raf-1 from the cytosol to the membrane. ET-18-OCH3 decreased the level of membrane-associated Raf-1 relative to untreated control cells. Since ET-18-OCH3 did not inhibit the activities of the kinases in the cascade, the reduced Raf-1 levels appeared to be the cause for the reduction in the magnitude and duration of MAPK activity. In this study we have investigated whether the reduced Raf-1 levels arise from a perturbation of the interaction of Raf-1 with activated Ras, which is the event that mediates the membrane recruitment. MATERIALS AND METHODS: The interaction of Raf-1 with Ras was examined by investigating the association of cytosolic Raf-1, from ET-18-OCH3-treated and untreated cells with purified GST-Ras-GTP-gamma-S bound to agarose beads. The level of associating Raf was determined by Western blot analysis. The effect of naturally occurring phospholipids on the Raf-1-Ras interaction was also examined to assess the specificity of the results. RESULTS: In cells preincubated with ET-18-OCH3, the interaction of GST-Ras-GTP-gamma-S with cytosolic Raf was reduced. The addition of ET-18-OCH3 to the cytosolic fraction isolated from untreated cells also reduced the binding of Raf to activated GST-Ras-GTP-gamma-S. Cytosolic Raf-1 from cells incubated with natural lysophospholipids was similar to that of controls. CONCLUSION: Our findings suggest that ET-18-OCH3 associates specifically with Raf-1 in the cytosol and interferes in the interaction of Raf-1 with activated Ras, thereby reducing the levels that are translocated to the membrane for activation. Thus Raf-1 appears to be a molecular target of ET-18-OCH3.
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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".