v-Src residues directly interacting with ligand and corresponding putative residues involved in Stat3 binding of the G-CSF receptor. v-Src residues which directly interact with the phosphorylated ligand were determined by observing the crystal structures of v-Src (Brookhaven accession codes 1SHA and 1SHB, with ligands pTyr-Val-Pro-Met and pTyr-Leu-Arg-Val, respectively) usingO59 with a 3.5 Å cut-off. The residues interacting with the central ligand are in white typeface in gray boxes, and the +3 residue of the ligand is shown in gray. The corresponding residues in the Stat3 model are shown in black typeface in white boxes, and the +3 residue is shown in black. Of note, the Stat3 residues proposed to interact with the phosphotyrosine are conserved or homologous to those in v-Src, but those defining the binding pocket for the +3 residue in Stat3 have hydrophilic substitutions that may hydrogen bond with the more hydrophilic G-CSF ligand.