出版社：American Society for Biochemistry and Molecular Biology
摘要：Recently, we reported that apoE inhibits platelet reactivity by stimulating NO release and postulated apoE-receptor activation of intracellular NO synthase (eNOS). Here, we implicate a low density lipoprotein receptor (LDL-R) family member by studying ligand requirements using purified apoE isoforms, synthetic peptides, and the receptor antagonist, receptor-associated protein (RAP). Then, using a homology cloning approach and degenerate PCR primers to amplify the conserved Cys-rich binding domain of the LDL-R family, this receptor was identified as LRP8 (formerly termed, apoER2), a newly described brain protein with several splice variants. Immunoprecipitation of platelet membranes with anti-peptide antisera confirmed protein expression, while analysis of RNA from platelets and two megakaryocytic cell lines (Meg-01 and HEL) disclosed that the major LRP8 transcript lacked binding repeats 4–6 (LRP8Δ4–6) but contained the full-length cytoplasmic tail. Sequence analysis of cytoplasmic LRP8 revealed several peptide motifs with potential for cellular signaling and we propose this as a rational mechanism through which apoE inhibits platelet aggregation.— Riddell, D. R., D. V. Vinogradov, A. K. Stannard, N. Chadwick, and J. S. Owen. Identification and characterization of LRP8 (apoER2) in human blood platelets. J. Lipid Res. 1999. 40: 1925–1930.
关键词：apolipoprotein E ; apolipoprotein E receptor 2 ; intracellular signalling ; LDL-receptor family ; nitric oxide ; platelet aggregation
