Following IL2 stimulation of IL2R, Shc is known to be tyrosine phosphorylated (Zhu et al. 1994). The identity of the kinase is uncertain (Gesbert et al. 1998); JAK1 may be responsible but this has not been demonstrated, another candidate is Lck.

Following IL-3 treatment, Shc becomes tyrosyl phoshorylated at 3 sites, Y427 (Salcini et al. 1994), Y349 and Y350 (Gotoh et al. 1996). Y427 mediates the subsequent association with Grb2 (Salcini et al. 1994).

Numbering here refers to Uniprot P29353 where the p66 isoform has been selected as the canonical form. Literature references used here refer to the p52 isoform which lacks the first 110 residues, so Y427 is referred to as Y317 in Salcini et al. 1994, Y349 and Y350 as Y239 and Y240 in Gotoh et al. 1996.