Cutting edge: TREM-like transcript-1, a platelet immunoreceptor tyrosine-based inhibition motif encoding costimulatory immunoreceptor that enhances, rather than inhibits, calcium signaling via SHP-2

J Immunol. 2004 May 15;172(10):5838-42. doi: 10.4049/jimmunol.172.10.5838.

Abstract

To date, immunoreceptor tyrosine-based inhibition motifs (ITIMs) have been shown to mediate inhibitory properties. We report a novel triggering receptor expressed on myeloid cells (TREM) family member, TREM-like transcript-1 (TLT1), which differs from the activating members because its cytoplasmic tail contains two ITIMs at Y245 and Y281. A TLT1 splice variant (TLT1sp) encodes a different cytoplasmic tail lacking ITIMs. Both isoforms are expressed in resting platelet alpha-granules, which are up-regulated to the cell surface following activation. TLT1 recruited Src homology 2 domain-containing tyrosine phosphatase (SHP)-2 to the "classical" ITIM (Y281) but not the "nonclassical" ITIM (Y245). In contrast to previously characterized ITIM receptors, TLT1 enhanced, rather than inhibited, FcepsilonRI-mediated calcium signaling in rat basophilic leukemia cells, a property dependent on the SHP-2 recruiting classical Y281 ITIM. Therefore, TLT1 represents a new costimulatory ITIM immunoreceptor and is the second ITIM-bearing receptor to be identified in platelets after platelet endothelial cell adhesion molecule-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Motifs / immunology
  • Animals
  • Blood Platelets / immunology*
  • Blood Platelets / metabolism*
  • Calcium Signaling / immunology*
  • Cell Line, Tumor
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cytoplasmic Granules / metabolism
  • Down-Regulation / immunology*
  • Gene Expression Regulation
  • Humans
  • Interphase / physiology
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / physiology*
  • Molecular Weight
  • P-Selectin / metabolism
  • Peptide Fragments / pharmacology
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatases / metabolism
  • Protein Tyrosine Phosphatases / physiology*
  • Rats
  • Receptors, IgE / physiology
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Receptors, Immunologic / physiology*
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Triggering Receptor Expressed on Myeloid Cells-1
  • Tyrosine / metabolism
  • Up-Regulation / immunology*
  • src Homology Domains / immunology

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • P-Selectin
  • Peptide Fragments
  • Protein Isoforms
  • Receptors, IgE
  • Receptors, Immunologic
  • TREM1 protein, human
  • Triggering Receptor Expressed on Myeloid Cells-1
  • thrombin receptor peptide SFLLRNP
  • Tyrosine
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, rat
  • SH2 Domain-Containing Protein Tyrosine Phosphatases