Protein Kinase C-Dependent Phosphorylation of Human Pleckstrin Reduces its Capacity for Self-Association and Impairs its Ability to Bind Phosphoinositide
Bibliographic record
Abstract
Pleckstrin is a major substrate of protein kinase C in lymphocytes, macrophages, monocytes, granulocytes and platelets. In these cells, pleckstrin is expressed at high levels and represents approximately 1 % of total cellular protein. Pleckstrin plays an important role in protein kinase C-dependent secretion, and abberant pleckstrin phosphorylation has been associated with disease. The mechanism, however, by which phosphorylation regulates pleckstrin function is unknown. Here, we show that native pleckstrin self-associates to form dimers that reduce its binding capacity to phosphoinositides. Phosphomimetic amino acid substitutions at residues normally phosphorylated by protein kinase C result in significantly reduced pleckstrin dimerization. Although phosphomimetic forms of pleckstrin exhibit subtle conformational changes they retain most of their phosphoinositide binding properties. These findings suggest that phosphorylation regulates pleckstrin interaction with membranes via a dimerization-dependent mechanism.
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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) | 0.000 | 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".