Neu (ErbB-2 erythroblastic leukemia viral oncogene homolog 2, HER-2, NGL, TKR1, c-erb B2) oncogene was originally cloned from a rat neuroglioblastoma. Human Neu is referred to as HER-2 since the protein structure resembles human epidermal growth factor receptor (HER). ErbB-2 refers to a high level of similarity to ErbB (avian erythroblastosis oncogene B), later found to code for EGFR (HER). Tyr 1248-phosphorylated Neu localizes with Mucin 4/sialomucin complex at the apical surfaces of ductal and alveolar cells in rodent lactating gland. Phosphorylation of Neu at Tyr 1139 promotes association of GRB2 and GRB7 through an Src homology 2 (SH2) domain-dependent interaction and contributes to the etiology of certain breast, gastric and esophageal cancers and testicular germ cell tumors. Neu phosphorylation on Tyr 1221 and Tyr 1248 promotes association of Shc (SH2 domain-containing transforming protein 1) through an SH2 domain. Neu phosphorylation at Tyr 1196 and Tyr 1248 promotes association of Shc through a PTB (phosphotyrosine binding) domain. SH2 and PTB domains recognize tyrosine phosphorylated proteins in a sequence-specific fashion and transduce extracellular signals via subcellular targeting, directing assembly of complexes and modulating enzymatic activity.
