PMID- 10508213
OWN - NLM
STAT- MEDLINE
DCOM- 19991223
LR  - 20131121
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 40
IP  - 10
DP  - 1999 Oct
TI  - Identification and characterization of LRP8 (apoER2) in human blood platelets.
PG  - 1925-30
AB  - 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 (LRP8delta4-6) 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.
FAU - Riddell, D R
AU  - Riddell DR
AD  - Department of Medicine, Royal Free and University College Medical School,
      University College London, Royal Free Campus, London NW3 2PF, United Kingdom.
FAU - Vinogradov, D V
AU  - Vinogradov DV
FAU - Stannard, A K
AU  - Stannard AK
FAU - Chadwick, N
AU  - Chadwick N
FAU - Owen, J S
AU  - Owen JS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Apolipoproteins E)
RN  - 0 (LDL-Receptor Related Proteins)
RN  - 0 (Lipoproteins, VLDL)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-1)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Lipoprotein)
RN  - 0 (low density lipoprotein receptor-related protein 8)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Apolipoproteins E/chemistry/pharmacology
MH  - Binding Sites
MH  - Blood Platelets/*metabolism
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Conserved Sequence
MH  - Cysteine
MH  - Humans
MH  - Hyperlipidemias/blood/genetics
MH  - Kinetics
MH  - LDL-Receptor Related Proteins
MH  - Lipoproteins, VLDL/blood
MH  - Low Density Lipoprotein Receptor-Related Protein-1
MH  - Megakaryocytes/metabolism
MH  - Peptide Fragments/chemistry
MH  - Platelet Aggregation
MH  - RNA, Messenger/genetics
MH  - Receptors, Immunologic/metabolism
MH  - Receptors, Lipoprotein/*blood/chemistry/*genetics
MH  - Transcription, Genetic
EDAT- 1999/10/03 00:00
MHDA- 1999/10/03 00:01
CRDT- 1999/10/03 00:00
PHST- 1999/10/03 00:00 [pubmed]
PHST- 1999/10/03 00:01 [medline]
PHST- 1999/10/03 00:00 [entrez]
PST - ppublish
SO  - J Lipid Res. 1999 Oct;40(10):1925-30.