Involvement of Lipid Rafts and Caveolae in gas6-Axl Signaling in Endothelial Cells
Bibliographic record
Abstract
Abstract Abstract 2211 Lipid rafts are localized regions of plasma membranes that contain primarily cholesterol and glycosphingolipids. Many receptor tyrosine kinases including the epidermal growth factor receptor, the platelet derived growth factor receptor, and the insulin receptor, localize specifically to these structures. Lipid rafts have been shown to play a role in intracellular signaling events. More specifically, diverse processes such as dimer formation, autophosphorylation, and intracellular adaptor protein recruitment/activation have been specifically involved in receptor tyrosine kinase/lipid raft interactions. Caveolae are defined as a subclass of lipid rafts and form well-shape invaginations on the cell surface. Caveolin-1 is the major constitutive protein of caveolae. Axl is a receptor tyrosine kinase whose association with lipid rafts and more specifically with caveolae has not been elucidated. Gas6, the ligand for Axl, is a vitamin K dependent protein that is post-translationally modified by an enzymatic process called g-carboxylation. We hypothesize that gas6/Axl mediated intracellular signaling is dependent on its localization to lipid rafts/caveolae in endothelial cells. First, we show that gas6-induced c-Src, Akt and ERK1/2 phosphorylation is mediated via Axl by using Axl siRNA in human umbilical vein endothelial cells (HUVECs). Then, lipid rafts were isolated from HUVECs by a detergent-free lysis method followed by a sucrose gradient centrifugation and western blot analysis. We found that Axl moved into the lipid raft-enriched fractions after 5 and 10 min of gas6 treatment as shown by its colocalization with caveolin-1. Interestingly, after gas6 treatment, c-Src, which is known to act as a transient docking platform for signaling molecules in lipid rafts, follow the same localization pattern to lipid raft-enriched fractions. The requirement of caveolae was then evaluated by transfecting HUVECs with caveolin-1 siRNA. Caveolin-1 knock down abolished completely gas6-induced phosphorylation of c-Src, Akt and ERK1/2 thus highlighting the role of caveolae in gas6-Axl signaling. Taken together these results demonstrate that activation of gas6-dependent signaling pathways involves Axl trafficking to lipid rafts/caveolae. These novel findings identify lipid rafts/caveolae as dynamic scaffolding systems for gas6/Axl interactions in endothelial cells. Disclosures: No relevant conflicts of interest to declare.
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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".