Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in U937 cells

Novel mechanisms for activated protein C cytoprotective activities involving noncanonical activation of protease-activated receptor 3

“…Other APC cofactors can possibly replace EPCR's cofactor function for PAR3 cleavage by APC on podocytes. [38][39][40] Alternatively, inflammatory mediators and various cytokines have known deleterious effects on EPCR expression and therefore, the effect on EPCR expression of continuous inclusion of interferon-g in the culture media of conditionally immortalized podocytes to keep them proliferating and undifferentiated is difficult to predict. 24,41,42 How do the APC-derived PAR3 tethered ligand peptides induce APC-like endothelial-and vascular-protective effects?…”

Up-regulation of ATP Binding Cassette Transporter A1 Expression by Very Low Density Lipoprotein Receptor and Apolipoprotein E Receptor 2

“…Upregulation of ABCA1 expression and augmentation of cholesterol efflux in macrophages could be a mechanism to offset the pro-atherogenic effect of VLDLR and apoER2 related to uptake of cholesterol-rich lipoproteins. In addition to macrophages, cells in vascular tissues, including endothelial cells and vascular smooth muscle cells, also express ABCA1 (34,35), VLDLR, and apoER2 (36,37). The ABCA1 protein expressed in these cells has been suggested to play a protective role against atherosclerosis (34,35).…”

Activated protein C: biased for translation

“…Thus, other PAR3-effector interactions are required for signal induction, diversification, and regulation ( Figure 3). PAR-effector complexes are hypothesized to involve the formation of PAR-PAR heterodimers and homodimers, 43 which may enable PARinduced transactivation of other PARs, integrate the transactivation of other GPCRs such as S1P1, 18,25,26 and incorporate cooperative cross talk with integrins such as Mac1 44,45 or other receptors such as ApoER2 46,47 or Tie2. 20,42,48 Formation of these complexes may achieve a signaling bias by promoting or discouraging the association of particular G-protein ensembles, 49,50 by recruiting b-arrestins, 30 or by incorporating nontraditional PAR signaling pathways via transactivations such as the activation of Tie2 by noncanonical activation of PAR3.…”