A number of receptors for lymphokines, hematopoietic growth factors and
growth hormone-related molecules have been found to share a common binding
domain. These receptors are designated as hematopoietin receptors
[2] and
the corresponding ligands as hematopoietins. Further, hematopoietins have been
subdivided into two major structural groups: Large/long and small/short
hematopoietins.
One subset of individual receptor chains that are part of receptor complexes
for small hematopoietins are structurally related such that their
extracellular parts strictly contain the 200 amino-acids hematopoietin
domain (duplicated in IL-3/-5/GM-CSF beta chain receptors KH97/AIC2B and
AIC2A). They define a structural subgroup containing the following chains:
- Interleukin-2 receptor beta chain (IL2RB)
- Interleukin-2 receptor common gamma chain (IL2RG)
- Interleukin-3 receptor beta chain (AIC2A)
- Interleukin-3/-5/GM-CSF receptor common beta chain (KH97/AIC2B)
- Interleukin-4 receptor alpha chain (IL4RA)
- Interleukin-7 receptor alpha chain (IL7RA)
- Interleukin-9 receptor alpha chain (IL9RA)
A schematic representation of the structure of these receptors is shown below:
+----------------------------------------xxxxxxx---------------------------+
| C C C C Extracellular XXXXXXX Cytoplasmic |
+-|-|-------|--|-------------------------xxxxxxx---------------------------+
| | | | Transmembrane
+-+ +--+
IL4RA, IL7RA and IL9RA are specific alpha chain receptors for IL-4, IL-7
and IL-9 respectively, whereas IL2RB is common to IL-2 and IL-15 (IL2RA and
IL15RA are not members of the hematopoietin receptor superfamily). IL2RG is
part of IL-2, IL-15, IL-7, IL-9 and IL-4 form I receptor complexes
[1].
KH97/AIC2B chain is part of GM-CSF, IL-3 and IL-5 receptor complexes and in
the mouse, AIC2B can be substituted by AIC2A, an IL-3 specific beta chain
receptor
[3]. Together with either IL13RA1 or IL13RA2, IL4RA is also part
of the IL-13 receptor complex for which IL-4 can compete with IL-13 (IL-4
receptor complex form II)
[4].
We have used one pattern to detect this subfamily. The motif is located at
the carboxy-terminal part of the 200 amino acid hematopoietin domain.