PMID- 25713122
OWN - NLM
STAT- MEDLINE
DCOM- 20160203
LR  - 20210217
IS  - 1535-9484 (Electronic)
IS  - 1535-9476 (Print)
IS  - 1535-9476 (Linking)
VI  - 14
IP  - 5
DP  - 2015 May
TI  - A Human Platelet Receptor Protein Microarray Identifies the High Affinity 
      Immunoglobulin E Receptor Subunit alpha (FcepsilonR1alpha) as an Activating Platelet 
      Endothelium Aggregation Receptor 1 (PEAR1) Ligand.
PG  - 1265-74
LID - 10.1074/mcp.M114.046946 [doi]
AB  - Genome-wide association studies to identify loci responsible for platelet 
      function and cardiovascular disease susceptibility have repeatedly identified 
      polymorphisms linked to a gene encoding platelet endothelium aggregation receptor 
      1 (PEAR1), an "orphan" cell surface receptor that is activated to stabilize 
      platelet aggregates. To investigate how PEAR1 signaling is initiated, we sought 
      to identify its extracellular ligand by creating a protein microarray 
      representing the secretome and receptor repertoire of the human platelet. Using 
      an avid soluble recombinant PEAR1 protein and a systematic screening assay 
      designed to detect extracellular interactions, we identified the high affinity 
      immunoglobulin E (IgE) receptor subunit alpha (FcepsilonR1alpha) as a PEAR1 ligand. FcepsilonR1alpha and 
      PEAR1 directly interacted through their membrane-proximal Ig-like and 13th 
      epidermal growth factor domains with a relatively strong affinity (KD  approximately  30 nm). 
      Precomplexing FcepsilonR1alpha with IgE potently inhibited the FcepsilonR1alpha-PEAR1 interaction, 
      and this was relieved by the anti-IgE therapeutic omalizumab. Oligomerized FcepsilonR1alpha 
      potentiated platelet aggregation and led to PEAR1 phosphorylation, an effect that 
      was also inhibited by IgE. These findings demonstrate how a protein microarray 
      resource can be used to gain important insight into the function of platelet 
      receptors and provide a mechanistic basis for the initiation of PEAR1 signaling 
      in platelet aggregation.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Sun, Yi
AU  - Sun Y
AD  - From the double daggerCell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, 
      Cambridge, CB10 1SA, United Kingdom and.
FAU - Vandenbriele, Christophe
AU  - Vandenbriele C
AD  -  section signCenter for Molecular and Vascular Biology, Department of Cardiovascular 
      Sciences, University of Leuven, Leuven 3000, Belgium.
FAU - Kauskot, Alexandre
AU  - Kauskot A
AD  -  section signCenter for Molecular and Vascular Biology, Department of Cardiovascular 
      Sciences, University of Leuven, Leuven 3000, Belgium.
FAU - Verhamme, Peter
AU  - Verhamme P
AD  -  section signCenter for Molecular and Vascular Biology, Department of Cardiovascular 
      Sciences, University of Leuven, Leuven 3000, Belgium.
FAU - Hoylaerts, Marc F
AU  - Hoylaerts MF
AD  -  section signCenter for Molecular and Vascular Biology, Department of Cardiovascular 
      Sciences, University of Leuven, Leuven 3000, Belgium.
FAU - Wright, Gavin J
AU  - Wright GJ
AD  - From the double daggerCell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, 
      Cambridge, CB10 1SA, United Kingdom and gw2@sanger.ac.uk.
LA  - eng
GR  - 098051/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150223
PL  - United States
TA  - Mol Cell Proteomics
JT  - Molecular & cellular proteomics : MCP
JID - 101125647
RN  - 0 (FcepsilonRI alpha-chain, human)
RN  - 0 (Ligands)
RN  - 0 (PEAR1 protein, human)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, IgE)
RN  - 0 (Recombinant Proteins)
RN  - 2P471X1Z11 (Omalizumab)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Binding Sites
MH  - Blood Platelets/cytology/*drug effects/metabolism
MH  - Gene Expression
MH  - HEK293 Cells
MH  - Humans
MH  - Immunoglobulin E/*chemistry/genetics
MH  - Kinetics
MH  - Ligands
MH  - Omalizumab/chemistry
MH  - Phosphorylation
MH  - Platelet Aggregation/*drug effects
MH  - Protein Array Analysis
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - Protein Multimerization
MH  - Protein Structure, Secondary
MH  - Receptors, Cell Surface/*chemistry/genetics
MH  - Receptors, IgE/*chemistry/genetics
MH  - Recombinant Proteins/chemistry/genetics/pharmacology
PMC - PMC4424398
EDAT- 2015/02/26 06:00
MHDA- 2016/02/04 06:00
PMCR- 2015/02/23
CRDT- 2015/02/26 06:00
PHST- 2014/11/27 00:00 [received]
PHST- 2015/02/26 06:00 [entrez]
PHST- 2015/02/26 06:00 [pubmed]
PHST- 2016/02/04 06:00 [medline]
PHST- 2015/02/23 00:00 [pmc-release]
AID - S1535-9476(20)32875-9 [pii]
AID - M114.046946 [pii]
AID - 10.1074/mcp.M114.046946 [doi]
PST - ppublish
SO  - Mol Cell Proteomics. 2015 May;14(5):1265-74. doi: 10.1074/mcp.M114.046946. Epub 
      2015 Feb 23.