Regulation of human platelet Rac1 activation through interaction with calmodulin
Bibliographic record
Abstract
Rac1 belongs to the Rho family of small GTP‐binding proteins and has been implicated in lamellipodia formation. Calmodulin (CaM), a ubiquitous Ca 2+ ‐binding protein, has been shown to interact with and regulate the activity of several small GTP‐binding proteins. In the present study, we have investigated if CaM interacts with Rac1 and regulates its activation. Thus, Rac1 was expressed as a GST fusion protein (GST‐Rac1). In vitro pull down assay demonstrated that CaM from platelet lysate interacts in a Ca 2+ ‐dependent manner with GST‐Rac1. In the reverse experiment, CaM coupled to Sepharose beads was used to pull down Rac1 from platelet lysate in a Ca 2+ ‐dependent manner. Pure CaM was also able interact with Rac1 demonstrating that Rac1‐CaM interaction was direct. Using CaM database analysis a 14 amino acid sequence in Rac1 was identified as the CaM binding region. The scrambled form of the peptide did not bind CaM. The role of CaM in Rac1 activation was investigated using freshly isolated human platelets. Maximal activation of platelet Rac1 in response to thrombin occurred at ∼60 sec. Incubation with the CaM inhibitor, W7, prior to thrombin challenge, abolished thrombin induced activation of platelet Rac1. The results demonstrate that in platelets, binding of CaM to Rac1 increases its activation and that CaM may play an important role in the regulation of cytoskeleton remodelling. Supported by Heart & Stroke Fdn of Manitoba.
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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".