Protein Kinase C Isoform-specific Differences in the Spatial-Temporal Regulation and Decoding of Metabotropic Glutamate Receptor1a-stimulated Second Messenger Responses
Bibliographic record
Abstract
Metabotropic glutamate receptors (mGluRs) coupled via Gq to the hydrolysis of phosphoinositides stimulate Ca(2+) and PKCbetaII oscillations in both excitable and non-excitable cells. In the present study, we show that mGluR1a activation stimulates the repetitive plasma membrane translocation of each of the conventional and novel, but not atypical, PKC isozymes. However, despite similarities in sequence and cofactor regulation by diacyglycerol and Ca(2+), conventional PKCs exhibit isoform-specific oscillation patterns. PKCalpha and PKCbetaI display three distinct patterns of activity: (1) agonist-independent oscillations, (2) agonist-stimulated oscillations, and (3) persistent plasma membrane localization in response to mGluR1a activation. In contrast, only agonist-stimulated PKCbetaII translocation responses are observed in mGluR1a-expressing cells. PKCbetaI expression also promotes persistent increases in intracellular diacyglycerol concentrations in response to mGluR1a stimulation without affecting PKCbetaII oscillation patterns in the same cell. PKCbetaII isoform-specific translocation patterns are regulated by specific amino acid residues localized within the C-terminal PKC V5 domain. Specifically, Asn-625 and Lys-668 localized within the V5 domain of PKCbetaII cooperatively suppress PKCbetaI-like response patterns for PKCbetaII. Thus, redundancy in PKC isoform expression and differential decoding of second messenger response provides a novel mechanism for generating cell type-specific responses to the same signal.
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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".