The EGF receptor family comprises several related receptor tyrosine kinases that are frequently overexpressed in a variety of carcinomas. Members of this receptor family include EGFR (HER1), Neu (ErbB-2, HER2), ErbB-3 (HER3) and ErbB-4 (HER4), which form either homodimers or heterodimers upon ligand binding. Full length ErbB-3 is overexpressed in human mammary tumors. The ErbB-3 gene also produces several alternative variants, including a secreted form which negatively regulates heregulin stimulated ErbB activation. ErbB-3 heterodimerizes with Neu and binds heregulin in order to activate phosphoinositide (PI) 3-kinase. The recruitment and activation of PI 3-kinase occurs via its interaction with phosphorylated YXXM motifs in the carboxy terminus of ErbB-3.