Tyrosine kinases are a large and diverse family of proteins found only in metazoans. The ERBB family, which encompasses subgroup I of the receptor tyrosine kinase (RTK) superfamily, has four members: epidermal growth factor receptor (EGFR)/ErbB1, ErbB2, ErbB3, and ErbB4. ERBB RTKs contain an extracellular domain that binds peptide ligands; they span the membrane once and have an intracellular portion with protein tyrosine kinase activity (Fig. 4.1). Ligand binding induces the formation of receptor dimers, and as a consequence the intrinsic kinase of the receptor is activated and transfers a phosphate group from the bound ATP to specific tyrosine side chains on the receptor proteins and on intracellular signaling proteins that bind the active RTKs. Subsequently, multiple signaling pathways become activated. The ERBB receptor/ligand family has been investigated in depth for many years, and comprehensive signaling maps describing the links between the plasma membrane receptors, the cytoplasmic signaling pathways, and the nucleus are available (Oda 2005).