TREM-Like Transcript-1, a Platelet Immunoreceptor Tyrosine-Based Inhibition Motif Encoding Costimulatory Immunoreceptor that Enhances, Rather than Inhibits, Calcium Signaling via SHP-2

• Published in: The Journal of immunology (1950) Vol. 172; no. 10; pp. 5838 - 5842
• Main Authors: Barrow, Alexander D, Astoul, Emmanuelle, Floto, Andres, Brooke, Gary, Relou, Ingrid AM, Jennings, Nicola S, Smith, Kenneth GC, Ouwehand, Willem, Farndale, Richard W, Alexander, Denis R, Trowsdale, John
• Format: Journal Article
• Language: English
• Published: 01.05.2004
• Subjects: platelet endothelial cell adhesion molecule-1; TLT-1 protein
• ISSN: 0022-1767

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, Fc epsilon RI-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.