P2Y nucleotide receptor signaling through MAPK/ERK is regulated by extracellular matrix: Involvement of β3 integrins
Bibliographic record
Abstract
Extracellular matrix influences cell behavior through receptors such as integrins and through transmission of mechanical forces. Nucleotides are released in response to mechanical stimuli and bind to P2 nucleotide receptors. As chondrocytes are subjected to frequent mechanical stimulation within a rich extracellular matrix, they are an excellent model for studying integration of signals induced by matrix and nucleotides. We investigated signaling of G protein-coupled P2Y receptors to MAPK/ERK and how this is influenced by matrix. Rat articular chondrocytes expressed transcripts for P2Y1, P2Y2, P2Y4, and P2Y6 receptors and responded to extracellular nucleotides by transient elevation of cytosolic calcium and MAPK/ERK phosphorylation. ERK1/2 activation was suppressed by the protein kinase C (PKC) inhibitors bisindolylmaleimide I and rottlerin, and by the phospholipase D inhibitor 1-butanol. Thus, nucleotides stimulate P2Y receptors to activate ERK1/2 through a mechanism dependent on PKC and phospholipase D. We next examined the involvement of integrins. Both an RGD-containing pentapeptide and a beta3 integrin blocking antibody, but not a beta1 integrin blocking antibody, abolished nucleotide-induced ERK1/2 phosphorylation. Moreover, chondrocytes adhering to fibronectin (which binds to beta1 and beta3 containing integrins in an RGD-dependent manner) displayed prolonged ERK1/2 signaling compared to cells grown on type I or II collagen (which bind to beta1-containing integrins in an RGD-independent manner). In conclusion, P2Y receptor signaling through ERK1/2 is gated selectively by matrix proteins. Thus, nucleotides released in response to mechanical stimulation will have differing effects on cell function due to changes in the composition of the extracellular matrix during development and disease.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".