6KR-EGFR expressing MCF7 following EGF or HRG stimulation

EGF and HRG, growth factor ligands for EGFR and ErbB3/4 receptor, induce transient and sustained ERK activity associated with cellular proliferation and differentiation of MCF-7 cells, respectively. To rigorously analyze the effect of ERK signal duration for mRNA expression dynamics and its relationship with cell determination, we modified the EGF-triggered ERK signal duration by changing the EGFR activation dynamics by impairing the ubiquitination and degradation process. Mutation of the six lysine residues (6KR; K692, K713, K730, K843, K905 and K946) of the EGFR responsible for ubiquitin conjugation has shown sustained phosphorylation of the receptor (Huang et al, 2006; Goh et al, 2010). Therefore we constructed the MCF-7 cell lines that stably express 6KR EGFR (6KR), and analyzed signaling and mRNA expression dynamics in response to EGF and HRG.

34

Nagashima T, Inoue N, Yumoto N, Saeki Y, Magi S, Volinsky N, Sorkin A, Kholodenko BN, Okada-Hatakeyama M