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.

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.
Mesh Terms:
Alternative Splicing, Amino Acid Motifs, Animals, Blood Platelets, Calcium Signaling, Cell Line, Tumor, Cell Membrane, Cytoplasmic Granules, Down-Regulation, Gene Expression Regulation, Humans, Interphase, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Molecular Weight, P-Selectin, Peptide Fragments, Protein Isoforms, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatases, Rats, Receptors, IgE, Receptors, Immunologic, SH2 Domain-Containing Protein Tyrosine Phosphatases, Tyrosine, Up-Regulation, src Homology Domains
J. Immunol.
Date: May. 15, 2004
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