130
Cytokines: Interleukins
Conserved
Ig-like
domaion
GPI
linkage
Fibronectin SH2
homology
Hematopoietin
receptor
domains
WSXWS
cysteines
motif
type III
domain
EPOR
GHR PRLR
IL-4R
IL-7R
IL-9R
IL-2R
b
IL-3R
AIC2A
KH97
AIC2B
IL-2R
g
IL-5R
a
IL-6R
a
IL-3R
a
GM-
CSFR
a
CNTFR
a
MPL
gp130
OSMR
LIFR
G-CSFR
100
Amino
acids
scale
Cytoplasmic
Extracellular
Fig. 3
Schematic receptor structures of the hematopoietin superfamily.
Modular elements are as shown in the box. (Reprinted with permission of
Cosman (1993)
Cytokine
5
, 95 Copyright Academic Press Ltd.)
with it. The high-afFnity receptor for IL-
12 is composed of two related ß-type
receptor chains, IL-12Rß1 and IL-12Rß2,
each independently having low afFnity for
IL-12. IL-12 p40 interacts primarily with IL-
12Rß1, while p35 interacts with IL-12Rß2.
IL-23, which contains the p40 subunit
in common with IL-12, is able to bind
only to IL-12Rß1, and probably a second,
as-yet unidentiFed, receptor subunit is
required to form the high-afFnity IL-23
receptor.
The
receptors
for
IL-10
and
related interleukins (IL-19, IL-20, IL-22,
IL-24, and IL-26) also have two subunits,
a long chain with a large intracellular
domain and a smaller accessory chain,
which have been classiFed on a structural
basis as type II cytokine receptors. The
latter, of which 12 members (cytokine
receptor family 2, CR±2-1 to CR±2-12) are
now characterized, include receptors for
interferons.
Unlike the
two
or three
component
receptors of most interleukins, there are
two distinct single-chain receptors for IL-
1 molecules. The Frst of these to be
characterized, now known as the type
I IL-1 receptor (IL-1RI), has widespread
tissue distribution and is found on T
cells, Fbroblasts, keratinocytes, endothelial
cells, synovial lining cells, chondrocytes,
and hepatocytes. The second receptor, the
type II IL-1 receptor (IL-1RII), is found
on B cells, neutrophils, and bone marrow
cells. The two receptors are about 40%
related in their N-terminal extracellular
domains, contain three immunoglobulin
(Ig)
loop
structures
and
are
therefore
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