Lighting up by EMARS

Abstract

Transmembrane proteins on the cell surface dynamically move in the sea of phospholipids. During the process of cell adhesion, migration and proliferation, physical interactions of transmembrane proteins such as integrins and receptor tyrosine kinases (RTKs) on the cell surface constantly vary. The enzyme-mediated activation of radical source (EMARS) reaction, a newly developed biochemical labelling method for cell surface molecules clustering in living cells, is a powerful tool for capturing new partners even if they only transiently cluster with the interesting target molecules during a biological process such as cell adhesion, migration, invasion or proliferation. The EMARS reaction was applied for investigating new partner RTKs to an adhesion molecule integrin β1, resulting in the identification of ErbB4. This study further reveals that the association of integrin β1 and ErbB4 occurs in a spatiotemporally regulated manner at an early phase within 2 h of seeding cells and that this induced activation of ErbB4 tyrosine kinase, which is required for integrin-dependent cell migration (Yamashita, R., Kotani, N., Ishiura, Y., Higahsiyama, S., and Honke, K. Spatiotemporally-regulated interaction between b1 integrin and ErbB4 that is involved in fibronectin-dependent cell migration. J Biochem 2011;149:347-355). The EMARS reaction is also currently lighting up intriguing new partners of target therapeutic molecules.