EGFR Phase Transition and the Corresponding Downstream Signaling

Chun-Wei Lin^1*

¹化學系, 國立清華大學, Hsinchu, Taiwan

* Presenter:Chun-Wei Lin, email:chunweilin@mx.nthu.edu.tw

Epidermal growth factor receptor (EGFR) is an important signaling protein on the membrane. It dictates the survival and the proliferation of the cell. EGFR implicated in many cancers shows over-expression, dysregulation, and hyperactivation. Recent studies have shown that the activation of EGFR involves the formation of the high-ordered multimer. To understand the mechanism of multimerization and the functionality of the multimer, EGFR is first in vitro reconstituted on the supported bilayer. Many downstream proteins are included in the isolated system to rebuild the signaling pathway of EGFR. Our study shows that the recruitment of the first downstream protein, Grb2, initiates the protein phase transition of EGFR on the supported lipid bilayer. The phase transition of EGFR is motivated by the dimerization of Grb2. The condensation of EGFR explains the formation of the high-ordered multimers observed in other studies. A more complicated reconstitution of EGFR signaling pathway further shows that the phase transition is required to amplify the propagation of the downstream signaling. In sum, our study demonstrates that receptor tyrosine kinase can undergo 2D phase transition on the membrane upon activation showing that the protein phase transition recently discovered in the biological system can be utilized in a diversity of ways by nature.

Keywords: membrane, cell signaling, EGFR, membrane protein, protein phase transition