Identification of a novel protein kinase A phosphorylation site, S449, on the delayed rectifier potassium channel, Kv1.2
Bibliographic record
Abstract
Our laboratory has provided evidence of the contribution of vascular smooth muscle (VSM) delayed rectifier potassium channels (K DR ), composed of Kv1.2, Kv1.5, Kv1.6 and Kvβ subunits, to the control of myogenic constriction of arterial resistance vessels. We have also shown that K DR channels in the vasculature are regulated by vasodilatory agonists acting through protein kinase A (PKA). However, the molecular basis for this regulation is uncertain. The current study used electrophysiological and biochemical analyses to identify PKA phosphorylation sites on Kv1.2. Heterologous expression of Kv1 channel subunits revealed that Kv1.2 currents were enhanced following stimulation of PKA, while Kv1.5 currents were unaffected. Previous studies suggested that Kv1.2 is phosphorylated by PKA at threonine‐46 (T46). However, several lines of evidence are inconsistent with this view. Mutation of T46 did not reduce phosphorylation of Kv1.2 by PKA in vitro . Phosphoamino acid analysis demonstrated that phosphorylation occurred exclusively at serine. Two‐dimensional (2D) phosphopeptide mapping revealed one major phosphopeptide, which was detected in both wild‐type and mutant Kv1.2. Mutation of serine‐449 (S449A) significantly reduced 32 P‐incorporation into Kv1.2. In vitro phosphorylation assays indicated that this site is stoichiometrically phosphorylated by PKA. Sequencing by mass spectrometry confirmed that Kv1.2 is phosphorylated by PKA at S449. This study suggests that S449 is a PKA phosphorylation site on Kv1.2, and provides insight into the mechanism underlying the modulation of VSM K DR by PKA.
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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 | 0.001 |
| 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 | 0.001 |
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".