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Detection of Cytokine and Growth Factor Receptor Dimerization Using Enzyme Fragment Complementation

Detection of Cytokine and Growth Factor Receptor Dimerization Using Enzyme Fragment Complementation
Version:
v122014

File Name/Number:
SLAS2014

Year:
2014

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Ligand-induced receptor dimerization is the first functional step in receptor activation, representing the most proximal, functional read-out for receptor activation. For the majority of Receptor Tyrosine Kinases these are homomultimer events whereas for cytokine receptor and other cell surface kinases these are typically heteromultimeric events. Standard cellular protein interaction techniques have not been able to faithfully monitor these interactions in a drug discovery setting. Here we present a novel application of the ProLink and EA complementation system to monitor native receptor-receptor interactions at the cell surface. We show that the technology is applicable across diverse receptor types such as the IL-17, TGFb, IL-5, Epo, ErbB4, and BMP family receptors. Further, we present quantitative data demonstrating ligand-dependent homo- and heterodimer formation for receptors previously thought to exist in preformed complexes, such as the EPO and IL-17 receptors. The high signal to noise, serum tolerance, and low CV’s make these assays applicable to small molecule discovery as well as a diverse range of antibody applications including functional characterization, QC and neutralizing antibody studies.