 The Erb-B HER receptor family consists of four transmembrane tyrosine kinases: Erb-B1-epithermal growth factor receptor EGFR, HER1, Erb-B2neu HER2, Erb-B3 HER3, and Erb-B4 HER4. The ectodomain of Erb-B1, Erb-B3, and Erb-B4 interacts with a specific set of ligand, whereas no ligand has been identified thus far for the Erb-B2 receptor. Nonetheless, Erb-B2 can be activated by any of the other ligand-activated Erb-B coreceptors. Upon ligand binding to the active domain of Erb-B1, Erb-B3, or Erb-B4, these receptors preferentially recruit Erb-B2 into a heterodimeric complex in which the Erb-B2 kinase can modulate receptor internalization and prolong signal transduction. 