PSTPIP Is a Substrate of PTP-PEST and Serves as a Scaffold Guiding PTP-PEST Toward a Specific Dephosphorylation of WASP
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Bibliographic record
Abstract
PSTPIP is a tyrosine-phosphorylated protein involved in the organization of the cytoskeleton. Its ectopic expression induces filipodial-like membrane extensions in NIH 3T3 cells. We previously observed a defect in cytokinesis and an increase in the tyrosine phosphorylation of PSTPIP in PTP-PEST-deficient fibroblasts. In this article, we demonstrate that PTP-PEST and PSTPIP are found in the same complexes in vivo and that they interact directly through the CTH domain of PTP-PEST and the coiled-coil domain of PSTPIP. We tested pathways that could regulate the tyrosine phosphorylation of PSTPIP. We found that the activation of the epidermal growth factor and platelet-derived growth factor receptors can induce PSTPIP phosphorylation. With the use of the PP2 inhibitor, we demonstrate that Src kinases are not involved in the epidermal growth factor-mediated phosphorylation of PSTPIP. Together with previous results, this suggests that c-Abl is the critical tyrosine kinase downstream of growth factor receptors responsible for PSTPIP phosphorylation. We also demonstrate that PTP-PEST dephosphorylates PSTPIP at tyrosine 344. Importantly, we identified tyrosine 344 as the main phosphorylation site of PSTPIP by performing tryptic phosphopeptide maps. This is an important finding since tyrosine 367 of PSTPIP was also proposed as a candidate phosphorylation site involved in the negative regulation of the association between PSTPIP and WASP. In this respect, we observed that the PSTPIP.WASP complex is stable in vivo and is not affected by the phosphorylation of PSTPIP. Furthermore, we demonstrate that PSTPIP serves as a scaffold protein between PTP-PEST and WASP and allows PTP-PEST to dephosphorylate WASP. This finding suggests a possible mechanism for PTP-PEST to directly modulate actin remodeling through the PSTPIP-WASP interaction.
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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) | 0.000 | 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 it