Biomedical Engineering Reference
In-Depth Information
Table 8.3
The cytokine receptor superfamilies. Refer to text for further details and to Table 8.1 for
explanation of cytokine abbreviations
Receptor superfamily name
Alternative name
Main members
The haematopoietic receptor superfamily
The cytokine receptor
superfamily
Receptors for:
IL-2-IL-7, IL-9, IL-12, G-CSF, GM-
CSF, EPO, LIF, CNTF, GH
The interferon receptor superfamily
Cytokine receptor type
II family
Receptors for:
IFN-
α
, -
β
, -
γ
, IL-10
The immunoglobulin superfamily
-
Receptors for:
IL-1, IL-6, FGF, PDGF, M-CSF
PTK receptor superfamily
-
Receptors for:
EGF, insulin, IGF-1
The nerve growth factor superfamily
-
Receptors for:
NGF, TGF
The seven transmembrane spanning receptor
superfamily
-
Receptors for various chemokines,
including IL-8 and MIP
The complement control protein superfamily
-
IL-2 receptor (α-chain)
were produced by a multicellular, anatomically distinguishable gland (e.g. the pancreas, the pituitary,
etc.) and functioned in a true endocrine fashion, affecting cells far distant from the site of their produc-
tion. Many initially described cytokines are produced by white blood cells (which do not constitute a
gland in the traditional sense of the word), and often function in an autocrine/paracrine manner.
However, even such distinguishing characteristics have become blurred. EPO, for example, is
produced in the kidney and liver and acts in an endocrine manner, promoting production of red
blood cells in the bone marrow. EPO could thus also be considered to be a true hormone.
8.1.1 Cytokine receptors
Recombinant DNA technology has also facilitated detailed study of cytokine receptors. Based
upon amino acid sequence homology, receptors are usually classifi ed as belonging to one of six
known superfamilies (Table 8.3). Individual members of any one superfamily characteristically
display 20-50 per cent homology. Conserved amino acids normally occur in discrete bands or
clusters, which usually correspond to a discrete domain in the receptor. Most receptors exhibit
multiple domains. In some cases a single receptor may contain domains characteristic of two or
more superfamilies. For example, the IL-6 receptor contains domains characteristic of both the
haematopoietic and immunoglobulin superfamilies, making it a member of both.
Some cytokine receptors are composed of a single transmembrane polypeptide (e.g. receptors
for IL-8, -9 and -10). Many contain two polypeptide components (including the IL-3, -4, and -5 re-
ceptors), and a few contain three or more polypeptide components (e.g. the IL-2 receptor contains
three polypeptide chains). In some instances a single cytokine may be capable of initiating signal
transduction by binding two or more distinct receptors (e.g. IL-1 has two distinct receptors (types
I and II), both of which are transmembrane glycoproteins).
In many cases where a receptor consists of multiple polypeptides, one of those polypeptides (which
will be unique to that receptor) will interact directly with the ligand. The additional polypeptide(s),
responsible for initiation of signal transduction, may be shared by a number of receptors (Figure 8.1).
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