EGFR CT domain P-site sequences.

The sequences surrounding each of the eight tyrosine residues in the EGFR CT domain are shown, with the tyrosine identifying the P-site highlighted in bold.Qualitative categorization based on the consensus of experiments characterizing major or minor sites of EGFR self-phosphorylation (see Table 2; -, phosphorylation not detected).Steady state catalytic efficiencies kcat/KM (in units of mM−1 min−1) characterizing the phosphorylation of synthetic peptide substrates containing the P-site sequences by the ligand-activated EGFR as determined by Fan et al.[8] (-, not determined).Predicted relative initial velocities of P-site self-phosphorylation computed as vphos = k′intra.(kcat/KM), where k′intra is relative frequency of binding site interactions for each P-site (the sums for those in both receiver and activator molecules) in simulations performed in the absence of CT domain electrostatic interactions (see Fig. 9 and Supporting Information, Text S1).