41) 救急車内施行の除細動により救命できた心室細動の一例(第131回日本循環器学会東海地方会)
Bibliographic record
Abstract
Sprouty-related EVH1 domain (Spred) proteins modulate growth factor receptor signaling by inhibiting the Ras/ERK pathway. In particular, the Sprouty-related domain (SPR) of Spred2 is essential for the Spred2-mediated inhibitory effect, but the molecular mechanism is largely unknown. We show here that the p85 subunit of phosphatidylinositol 3-kinase (PI3K) is a new binding partner of Spred2 via interaction with the SPR domain. Mutation of three tyrosines 303/343/353 within the SPR domain not only abolish EGF-induced p85 binding to Spred2 but also attenuate the inhibitory effect on Ras/ERK activation by Spred2. This results in increased Hela cell proliferation and neurite outgrowth in PC12 cells. We further demonstrate that p85 binding to Spred2 enhances the Spred2-mediated inhibitory effect via increased Ras binding to Spred2 and decreased Spred2 ubiquitination. We also show that Spred2 constitutively associates with epidermal growth factor receptor (EGFR) via its SPR domain and dissociates from EGFR upon EGF stimulation. Moreover, mutation of tyrosines 303/343/353 together enhances Spred2 binding to EGFR. Taken together, these results suggest critical roles of the three tyrosines 303/343/353 within the SPR domain in regulating Spred2 signaling and provide a mechanism for the SPR domain of Spred2 to mediate the inhibitory effect on the Ras/ERK pathway.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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".