PathwayStep548 PathwayStep549 PathwayStep547 PathwayStep553 PathwayStep554 PathwayStep551 PathwayStep552 PathwayStep550 LDL binds to LRP8 FGR binds and phosphorylates LRP8 Fgr may phosphorylate p38 MAPK Phosphorylation of cPLA2 by MAPK p38 alpha PECAM-1 binds PP2A LDL leads to activation of PECAM1 Interaction of PECAM-1 and SHP-2 Interaction of PECAM-1 and SHP-1 Platelet sensitization by LDL Authored: Akkerman, JW, 2009-09-04 Edited: Jupe, S, 2010-06-07 Physiological concentrations (1g/L) of Low density lipoprotein (LDL) enhance platelet aggregation responses initiated by thrombin, collagen, and ADP. This enhancement involves the rapid phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) at Thr180 and Tyr182. The receptor for LDL is ApoER2, a splice variant of the classical ApoE receptor. ApoER2 stimulation leads to association of the Src family kinase Fgr which is probably responsible for subsequent phosphorylation of p38MAPK. This stimulation is transient because LDL also increases the activity of PECAM-1, which stimulates phosphatases that dephosphorylate p38MAPK. Pubmed12038793 Pubmed12775720 Pubmed15459198 Reactome Database ID Release 43432142 Reactome, http://www.reactome.org ReactomeREACT_23879 Reviewed: Kunapuli, SP, 2010-06-07