Rho‐associated kinase and zipper‐interacting protein kinase: roles in rapid phosphorylation events in serum‐stimulated human arterial smooth muscle cells
Bibliographic record
Abstract
Myosin regulatory light chain (LC 20 ) phosphorylation plays an important role in vascular smooth muscle contraction and cell migration. Rho‐associated kinase (ROCK) and zipper‐interacting protein kinase (ZIPK) have been implicated in the regulation of LC 20 phosphorylation via direct phosphorylation of LC 20 and indirectly via phosphorylation of MYPT1 (the myosin targeting subunit of myosin light chain phosphatase, MLCP) and Par‐4 (prostate‐apoptosis response‐4). Phosphorylation of MYPT1 at T696 and T850 inhibits MLCP activity whereas phosphorylation of Par‐4 at T163 disrupts its interaction with MYPT1, exposing the sites of phosphorylation in MYPT1 and leading to MLCP inhibition. To evaluate the roles of ROCK and ZIPK in these rapid serum‐induced phosphorylation events, we investigated the time‐courses of phosphorylation of LC 20 , MYPT1 and Par‐4 in serum‐stimulated human vascular smooth muscle cells, and examined the effects of siRNA‐mediated ROCK and ZIPK knockdown and pharmacological inhibition on these phosphorylation events. Serum stimulation induced rapid phosphorylation of LC 20 at T18 and S19, MYPT1 at T696 and T850, and Par‐4 at T163, peaking within 30–120 s. ROCK1 knockdown decreased the levels of phosphorylation of LC 20 , MYPT1 and Par‐4, whereas ZIPK knockdown decreased LC 20 phosphorylation, but increased phosphorylation of MYPT1 and Par‐4. Consistent with the effects of kinase knockdown, ROCK inhibition by GSK429286A and H1152 reduced serum‐induced LC 20 , MYPT1 and Par‐4 phosphorylation, while ZIPK inhibition by HS38 reduced only LC 20 phosphorylation. We conclude that (i) serum stimulation of cultured human arterial smooth muscle cells results in rapid phosphorylation of LC 20 , MYPT1 and Par‐4, (ii) both ROCK and ZIPK are involved in LC 20 phosphorylation, and (iii) only ROCK accounts for MYPT1 and Par‐4 phosphorylation. Support or Funding Information Supported by a grant from the Canadian Institutes of Health Research (MOP‐111262).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".