Figure 6.

Effect of the E909G mutation on the allosteric activator function of HER3. (A) Diagram showing the cluster of charged residues in the vicinity of HER3 Glu⁹⁰⁹ at the activator/receiver interface of the EGFR/HER3 dimer (left) and in the EGFR/HER3-E909G dimer (right). (B) Activity of the EGFR-V924R kinase domain in the presence of the indicated HER3 kinase domain constructs in the vesicle-based assay. (C) Activity of the EGFR-V924R kinase domain upon titration with the wild-type (WT, blue) or E909G (red) HER3 kinase domain. Both EGFR and HER3 contained the kinase domains and the full JM segments. (D) The activity of the EGFR-V924R kinase domain without additional mutation (WT) or with the indicated mutation in the presence of the wild-type HER3 kinase domain in the vesicle-based assay. (E) Sequence conservation of amino acid residues in the acidic cluster surrounding Glu⁹⁰⁹. (F) Activity of the EGFR-V924R kinase domain in the presence of the HERG1-I682Q kinase domain containing either no additional mutations (WT) or the E907G mutation in the vesicle-based assay. In panels B, C, D, and F, data are plotted as the mean and standard deviation of three independent experiments, *p<0.005, **p<0.001.