Receptor tyrosine kinases (RTKs) control cell growth, proliferation, and differentiation. Aberrant RTK signaling is at the heart of many diseases connected to development and growth. For example, epidermal growth factor receptor (EGFR or ErbB1) is linked to tumorigenesis, most notably in lung cancer, for which several FDA-approved EGFR inhibitors have been developed. Recently, we used PIE-FCCS to resolve multiple dimerization interfaces for EphA2, an RTK upregulated in many cancer types. We connected the dimerization interfaces to different downstream signaling effects in vitro and even tumor growth, metastasis, and overall survival in vivo.

• Shi, X.; Lingerak, R.; Herting, C. J.; Ge, Y.; Kim, S.; Toth, P.; Wang, W.; Brown, B. P.; Meiler, J.; Sossey-Alaoui, K.; et al. Time-resolved live-cell spectroscopy reveals EphA2 multimeric assembly. Science 2023, 382 (6674), 1042-1050. DOI: https://doi.org/10.1126/science.adg5314.

• Rybak, J. A.; Sahoo, A. R.; Kim, S.; Pyron, R. J.; Pitts, S. B.; Guleryuz, S.; Smith, A. W.; Buck, M.; Barrera, F. N. Allosteric inhibition of the epidermal growth factor receptor through disruption of transmembrane interactions. J Biol Chem 2023, 104914. DOI: https://doi.org/10.1016/j.jbc.2023.104914.

• Huang, Y.; Bharill, S.; Karandur, D.; Peterson, S. M.; Marita, M.; Shi, X.; Kaliszewski, M. J.; Smith, A. W.; Isacoff, E. Y.; Kuriyan, J. Molecular basis for multimerization in the activation of the epidermal growth factor receptor. eLife 2016, 5, e14107. DOI: https://doi.org/10.7554/eLife.14107.