Triggering receptors expressed on myeloid cells (TREM)

Published on February 13, 2013   69 min

A selection of talks on Immunology

0:00
Hello. My name is Dan McVicar. I'm a Senior Investigator in the Cancer and Inflammation Program at the National Cancer Institute. I'm going to be talking today about the triggering receptors expressed on myeloid cells or the TREM. I think you'll find this to be a very interesting family of receptors that's involved in many facets of immune regulation. Because it is such a broad and wide topic, as I review it for you here, I'm not going to be able to cover everything. I want to apologize in advance to those authors whose work I'm not able to specifically show you as I introduce you to this intriguing gene family.
0:35
I'm going to break the presentation down into four parts. First of all, talk briefly about the discovery of this receptor family. Then we'll look at the locus and the structure of the proteins within this receptor family. Then I'll take you one by one through descriptions of most of the family members of the family. Lastly, I'll give you a few final comments and some outstanding questions that we're thinking about as we look at this receptor family.
1:01
In order to appreciate the TREM and where they came from, really, one has to know a little bit about this signaling molecule called DAP12. It's encoded by the gene TYROBP. DAP12 was initially detected as a co-precipitating protein with activating Ly49s and KIR. These are the Class one recognition receptors that NK cells use to detect self from non-self. It has a molecular weight of about 12 kiloDaltons, as you would imagine by the name. It's a disulfide-linked dimer, and it shifts up to about 32 kiloDaltons upon tyrosine phosphorylation. It was cloned, but based on its biochemical similarity to the TCR zeta chain and the Fc Epsilon Gamma chain by the Lanier Lab in 1998. The protein has a very small extracellular domain, and it has a negatively charged transmembrane domain due to an aspartic acid residue. Each molecule has a single tyrosine-based immunoreceptor activation motif or ITAM. This is a motif that has two tyrosines and configuration for phosphorylation that are followed at the plus three-position by a leucine or other hydrophobic residue. As tyrosines are carefully spaced so that they fit perfectly into the SH2 domains of the SIK, namely tyrosine kinases, which are the tyrosine kinases that mediate DAP12 signaling. DAP 12 is expressed on natural killer cells, of course, but is extensively expressed within the myeloid compartment and that's where we're going to be talking about it today. I should also point out that there is a full presentation on DAP12 by Eric Vivier in this series, and I recommend that you take a look at that.
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Triggering receptors expressed on myeloid cells (TREM)

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