Regulation of protein phosphatase 1 alpha subcellular localization by 14-3-3 zeta
Bibliographic record
Abstract
Protein phosphatases have several substrates that are involved in many processes in mammalian cells such as glycogen metabolism, cell cycle progression, cell differentiation, apoptosis, protein synthesis and signal transduction (Cohen, 2002; Berndt, 1999; Shenolikar, 1994) The alpha isoform of protein phosphatase 1 (PP1) may play a significant role in neuronal differentiation. While the extent of phosphorylation of PP1 has been shown to affect the degree of differentiation of nerve growth factor (NGF)-treated PC12 cells, it is not known whether phosphorylation of PP1 alpha is needed for its interaction with 14-3-3 as has been suggested for PP1 gamma binding to 14-3-3. 14-3-3 proteins are phosphoproteins that can regulate the subcellular localization, phosphorylation state, stability and protein-protein interactions of their target upon binding. A greater understanding of the interaction of PP1 and 14-3-3 during neuronal differentiation is necessary to fully appreciate the cell signaling cascade that is triggered during neuronal differentiation. By performing GST pull-downs and co-immunoprecipitation experiments, we found that PP1 and 14-3-3 interact independently of threonine 320 (T320) phosphorylation. In addition, fractionation of nuclear and cytoplasmic proteins in HEK293T cells demonstrates that the subcellular localization of PP1 is affected by the presence of 14-3-3. From pull-downs using PP1 deletion mutants, we suggest that the C-terminus of PP1 is important for the interaction between PP1 and 14-3-3. The results provide new insight on how the regulation of PP1 by 14-3-3 binding may affect the nucleocytoplasmic shuttling of PP1 during neuronal differentiation of PC12 cells.
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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) | 0.002 | 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".