Lipid Phosphate Phosphatase-1 Regulates Lysophosphatidate-induced Fibroblast Migration by Controlling Phospholipase D2-dependent Phosphatidate Generation
Bibliographic record
Abstract
Lysophosphatidate (LPA) stimulates cell migration and division through a family of G-protein-coupled receptors. Lipid phosphate phosphatase-1 (LPP1) regulates the degradation of extracellular LPA as well as the intracellular accumulation of lipid phosphates. Here we show that increasing the catalytic activity of LPP1 decreased the pertussis toxin-sensitive stimulation of fibroblast migration by LPA and an LPA-receptor agonist that could not be dephosphorylated. Conversely, knockdown of endogenous LPP1 activity increased LPA-induced migration. However, LPP1 did not affect PDGF- or endothelin-induced migration of fibroblasts in Transwell chamber and "wound healing" assays. Thus, in addition to degrading exogenous LPA, LPP1 controls signaling downstream of LPA receptors. Consistent with this conclusion, LPP1 expression decreased phospholipase D (PLD) stimulation by LPA and PDGF, and phosphatidate accumulation. This LPP1 effect was upstream of PLD activation in addition to the possible metabolism of phosphatidate to diacylglycerol. PLD(2) activation was necessary for LPA-, but not PDGF-induced migration. Increased LPP1 expression also decreased the LPA-, but not the PDGF-induced activation of important proteins involved in fibroblast migration. These included decreased LPA-induced activation of ERK and Rho, and the basal activities of Rac and Cdc42. However, ERK and Rho activation were not downstream targets of LPA-induced PLD(2) activity. We conclude that the intracellular actions of LPP1 play important functions in regulating LPA-induced fibroblast migration through PLD2. LPP1 also controls PDGF-induced phosphatidate formation. These results shed new light on the roles of LPP1 in controlling wound healing and the growth and metastasis of tumors.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 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".