Early platelet activation by low density lipoprotein via p38MAP kinase.

Low Density Lipoprotein (LDL) is known to sensitize platelets for physiological agonists. To clarify the basis of this sensitization, we investigated the involvement of p38MAP Kinase (p38MAPK). As dual phosphorylation on Thr180 and Tyr182 of p38MAPK is the trigger for activation of the kinase, p38MAPK-activity was measured with an antibody that recognizes the dual-phosphorylated sequence.

Low-density lipoprotein enhances platelet secretion via integrin-alphaIIbbeta3-mediated signaling.

LDL is known to increase the sensitivity of human platelets for agonists and to induce aggregation and secretion independently at high concentrations, but its mechanism of action is largely obscure. To clarify how LDL increases platelet sensitivity, cells were incubated in lipoprotein-poor plasma and treated with collagen at a concentration that induced approximately 20% secretion of 14C-serotonin. Preincubation with LDL (30 minutes at 37 degreesC) enhanced secretion in a dose-dependent manner to 60+/-14% at a concentration of 2 g LDL protein/L.

Low density lipoprotein phosphorylates the focal adhesion-associated kinase p125(FAK) in human platelets independent of integrin alphaIIb beta3.

Low density lipoprotein (LDL) is known to sensitize platelets to agonists via integrin mediated outside-in signaling (Hackeng, C. M., Huigsloot, M.

The 39-kDa receptor-associated protein modulates lipoprotein catabolism by binding to LDL receptors.

The 39-kDa receptor-associated protein (RAP) is cosynthesized and co-purifies with the low density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin receptor and is thought to modulate ligand binding to LRP. In addition to binding LRP, RAP binds two other members of the low density lipoprotein (LDL) receptor family, gp330 and very low density lipoprotein (VLDL) receptors. Here, we show that RAP binds to LDL receptors as well.