Biology Reference
In-Depth Information
T A B L E
14.1. Cytokine Receptor Families and Their Ligands
Cytokine Receptors
Cytokines
Ig superfamily
IL-1, IL-6, PDGF, FGF, M-CSF
Type I ( WSXWS)
IL-6, IL-2 (b and g chains), IL-3, IL-4, IL-5, IL-6, IL-7,
G-CSF, GM-CSF
Type II
IFNs (a, b, g)
Type III
TNF-a (p55, p75)
7 TMD-R
chemokines
Multi protein complex
IL-2 (a, b, g), IL-6 (IL-6R gp130), IL-3 (IL-3R gp150)
Underlined cytokines utilize di¨erent classes of receptors.
eral cytokine mRNAs with limited amounts of biological samples, and there-
fore these methods are of particular interest in clinical settings.
CYTOKINE RECEPTORS
Cytokine receptors are commonly subdivided into ®ve families based on their
secondary structural domains ( Table 14.1). The ®rst family contains di¨erent
extracellular domains (1±3) belonging to the immunoglobulin (Ig) superfamily.
In addition to classic cytokines, like IL-1 and IL-6, both macrophage colony-
stimulating factor (M-CSF ) and growth factors such as platelet-derived growth
factor (PDGF ) and ®broblast growth factor ( FGF ) utilize these receptors.
The second cytokine receptor group, one of the largest families, and also
termed ``type I'' cytokine receptors, is characterized by an extracellular sequence
of ®ve amino acids (tryptophan-serine-X-tryptophan-serin or WSXWS) in close
proximity to the transmembrane region of the receptor. An Ig and a WSXWS
domain also characterize the IL-6 receptor.
The third group of molecules, ``type II'' cytokine receptors, is characterized
only by its primary sequence. Type II receptors are typically used by IFNs.
TNF/Nerve growth factor ( NGF ) receptors are also called ``type III'' cyto-
kine receptors and encompass several regulatory molecules such as CD27,
CD30, and CD40. Some members, FAS (CD95) and the p55 TNF receptor,
possess a ``death intracellular domain'' delivering apoptotic signals to the cells.
The ®fth family of cytokine receptors consists of seven transmembrane do-
main receptors, the largest receptor family identi®ed in nature, comprising the
chemokine receptors.
Finally, many cytokine receptors are complexes of di¨erent transmembrane
proteins. For example, the IL-2 receptor has three subunits named a, b, and g.
b and g subunits contain the WSXWS domain and are responsible for binding
and signal transduction; their association with the a subunit (CD25) increases
the binding a½nity for IL-2 (Minami et al., 1993). The IL-6 receptor interacts
with a transmembrane protein, characterized by an Ig and WSXWS domain.
