Homology of the ATP binding pocket of known imatinib-sensitive and selected TKs important for immunoreceptor signaling. (A) Protein sequences of the ATP binding pockets of the known imatinib-sensitive TKs (underlined), and related kinases important for immunoreceptor signaling were aligned using Multalin software. The 6 amino acid residues known to interact directly with imatinib are boxed and numbered as they appear in ABL (arrows). Three TKs important for immunoreceptor signaling that share homology in all residues, including the critical threonine 315, are highlighted by an asterisk. ZAP70 has been added for comparison. (B) LCK in vitro tyrosine kinase assay with serial 4-fold dilutions of imatinib from 100 μM to 0.025 μM, given on the x-axis in logarithmic scale. The ATP concentration, which decreases with increasing tyrosine kinase activity, is measured as relative light units (RLUs), shown on the y-axis. Values are mean of triplicates. IC50 for imatinib is 0.8 μM(R2 = 0.99).
