Abstract Ligand-induced receptor dimerization is the first functional step in receptor signaling, representing the most proximal, functional read-out for receptor activation. Here we present a novel application of the Enzyme Fragment Complementation system to monitor receptor-receptor interactions at the surface of intact cells, applicable to diverse receptor types such as RTKs, Interleukin receptors, BMP receptors and cytokine receptors, amongst others. For the purpose of this poster, we will focus on the HER family of receptors. It is well understood that the HER family proteins can dimerize with the other members of its family leading to a complicated oncogenic signaling cascade. Surprisingly, existing cellular assays have been unable to faithfully monitor these interactions proximally in a drug discovery setting. We present EFC-based cellular assays that monitor EGFR homodimerization, EGFR-ErbB2 and ErbB2-ErbB3 heterodimerization events at the receptor. The high signal to noise ratio, serum tolerance and reproducibility make these assays ideal for a diverse range of applications for the identification and development of therapeutic small molecules and biologics, including screening, functional characterization, QC lot release assays and neutralizing antibody studies. Citation Format: Jane Lamerdin, Abhishek Saharia, Jennifer Lin-Jones, Mimi Nguyen, Hyna Fabionar, Sangeetha Gunturi, Abha Srivastava, Tom Wehrman. Detection of EGFR, HER2, HER3 and HER4 homodimerization and heterodimerization using EFC-based cellular assays. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3742. doi:10.1158/1538-7445.AM2014-3742
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