Signalling co-receptors
In addition to the three groups of signalling receptors discussed above, there is a group
of membrane receptors that bind agonists but which do not directly transduce a
cellular signal but to do so they form a complex with a receptor from one of the
above three classes. These receptors are termedco-receptorsoraccessory receptors.
These co-receptors are:- used by a large number of ligands including interleukin, epidermal growth factor and
fibroblast growth factor; - expressed ubiquitously within a given organism such that they are often the most
abundant receptor for the agonists they bind; - expressed with conserved structural features on the cell surface of a diverse range of
organisms.
Eight families of co-receptors have been identified, each containing up to eight
members. The agonists that they bind are promiscuous in that a given co-receptor
may bind up to nine different agonists and a given agonist can bind to more than
one co-receptor. Their central role in the regulation of cellular processes is evident
from the observation that their mutation and/or altered expression is associated with
such human diseases as certain cancers, inflammation and ischaemic heart disease.
Mutations commonly cause a loss of co-receptor function leading to an autosomal
dominant or recessive inherited disorder (see cytokine receptors, Section 17.4.4).17.2 Quantitative aspects of receptor–ligand binding
17.2.1 Dose–response curves
The response of membrane receptors in their resting inactive state to exposure to an
increasing concentration (dose) of agonist is a curve that has three distinct regions:- an initial threshold below which little or no response is observed;
- a slope in which the response increases rapidly with increasing dose;
- a declining response with further increases in dose and a final maximum response.
Since such plots commonly span several hundred-fold variations in agonist concen-
tration, they are best expressed in semi-logarithmic form (Fig. 17.1).
A dose–response curve for an inverse agonist (Section 17.2.2) acting on a receptor
with constitutive activity would be a mirror image of that shown in Fig. 17.1 resulting
in a progressive decrease in receptor activity.
Dose–response studies coupled with the observed transduction pathway have
enabled molecules (ligands) that bind to a receptor to be placed into one or more of
the following classes: - Full agonists: These ligands increase the activity of the receptors and produce the
same maximal response but they differ in the dose required to achieve it (Fig. 17.1).
663 17.2 Quantitative aspects of receptor–ligand binding