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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.
