Bibliographic record
Abstract
It is well established that EGFR signals from both the plasma membrane (PM) and endosome (EN). However, very little is known about whether and how the EGFR signals at the PM and EN to differentially regulate various signaling pathways and the physiological outcomes. In this communication, we established a system that allowed the specific activations of EGFR at different cell locations: PM and EN. PM activation of EGFR is achieved by activation of endocytosis-deficient mutant EGFR1010LL/AA stably expressed in CHO cells (CHO-LL/AA cell). EN activation of EGFR is achieved by activating the wild type EGFR stably expressed in CHO cells (CHO-EGFR cell) after its internalization into EN with a previously reported protocol. We showed that both EGFR activations at PM and EN activated ERK to a similar level, but differentially stimulated transcriptional factors c-jun and c-fos. We further showed that EGFR activations at PM and EN resulted in differential spatio-temporal dynamics of phosphorylated ERK which caused the differential activation of two downstream substrates ELK1 and RSK. Finally we showed that EGFR signaling from PM and EN led to different physiological outcomes. CHO-LL/AA cells that only generate PM EGFR signals have a larger cell size and slower proliferation rate than CHO-EGFR cells. We conclude that location-specific EGFR activation differentially regulates cell functions through a spatio-temporal interplay of ERK activation.
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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) | 0.004 | 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".