Hepatocyte Growth Factor Regulated Tyrosine Kinase Substrate (HGS)

The deduced amino acid sequence of HGS, which the authors symbolized HRS, was found to be 93% homologous to that of mouse Hrs. HGS contains double zinc finger (FYVE) motifs, a putative coiled-coil sequence, and nucleotide-binding sites. Northern blot analysis detected expression of HGS in lymphoid and nonlymphoid tissues. Immunoblotting, however, determined that the phosphorylated species was found after but not before IL2 stimulation. Irrespective of IL2 stimulation, HGS coimmunoprecipitated with STAM, a signal-transducing adaptor molecule that is directly associated with and phosphorylated by JAK3 and JAK2 upon stimulation with IL2 and GMCSF, respectively. A mouse Hrs mutant from which the coiled-coil sequence was deleted lost STAM binding activity.