A Human Platelet Receptor Protein Microarray Identifies the High Affinity Immunoglobulin E Receptor Subunit α (FcεR1α) as an Activating Platelet Endothelium Aggregation Receptor 1 (PEAR1) Ligand

Mol Cell Proteomics. 2015 May;14(5):1265-74. doi: 10.1074/mcp.M114.046946. Epub 2015 Feb 23.


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 α (FcεR1α) as a PEAR1 ligand. FcεR1α and PEAR1 directly interacted through their membrane-proximal Ig-like and 13th epidermal growth factor domains with a relatively strong affinity (KD ∼ 30 nm). Precomplexing FcεR1α with IgE potently inhibited the FcεR1α-PEAR1 interaction, and this was relieved by the anti-IgE therapeutic omalizumab. Oligomerized FcεR1α 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Immunoglobulin E / chemistry*
  • Immunoglobulin E / genetics
  • Kinetics
  • Ligands
  • Omalizumab / chemistry
  • Phosphorylation
  • Platelet Aggregation / drug effects*
  • Protein Array Analysis
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Protein Structure, Secondary
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / genetics
  • Receptors, IgE / chemistry*
  • Receptors, IgE / genetics
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology


  • FcepsilonRI alpha-chain, human
  • Ligands
  • PEAR1 protein, human
  • Receptors, Cell Surface
  • Receptors, IgE
  • Recombinant Proteins
  • Omalizumab
  • Immunoglobulin E