A unified model of c-erbB receptor homo- and heterodimerisation.
The c-erbB receptor tyrosine kinase family plays an important role in cell regulation. Receptor activation proceeds by the formation of receptor homo- and/or hetero-dimers and is promoted by the binding of a cognate ligand at the cell surface. While some experimental work has demonstrated that the formation of heterodimers can influence a cellular response, the extent of heterodimerisation has not been accurately assessed: the assortment of receptors and ligands gives rise to a complex combinatorial system for which intuitive prediction of homo- and hetero-dimerisation is difficult. We present a mathematical model which combines observations for homo-dimerisation with the additional interactions arising from the presence of multiple c-erbB receptors. We provide a simple explanation for the apparently conflicting results for binding studies carried out with either solubilised receptors, vesicles or cells and our model predicts binding behaviour which is compatible with published experimental findings for cells expressing either one or two c-erbB receptors. This model establishes the basis for interpretation of ligand binding experiments, where variations in the apparent ligand affinity can be attributed to changes in receptor expression or ligand preferences according to the binding profile.
Chamberlin
S G
SG
CRC Wessex Medical Oncology Unit, Southampton General Hospital, UK. sgc@chem.ufl.edu
Davies
D E
DE
D001667:Binding, Competitive; D019281:Dimerization; D066246:ErbB Receptors / Q000737:chemistry*; D008024:Ligands; D008956:Models, Chemical
D008024:Ligands; D066246:ErbB Receptors