ErbB4

ErbB4, also called Her4 (human epidermal growth factor receptor 4), is a type I membrane glycoprotein that is a member of the ErbB family of tyrosine kinase receptors. ErbB family members serve as receptors for the epidermal growth factor (EGF) family of growth factors. ErbB4 is expressed in normal skeletal muscle, heart, pituitary, brain and several breast carcinomas. ErbB4 ligands include the neuregulins, betacellulin and heparin-binding EGF-like growth factor (HB-EGF) . Monomeric ErbB4 binds its ligands with low affinity. Typically, heterodimerization with ErbB2 forms the high affinity receptor complex. However, ErbB4 has also been shown to heterodimerize with both ErbB1 and ErbB3. It has been suggested that the identity of the ligand may influence the dimerization partner. Several ErbB4 isoforms exist. Two of these differ in the presence of juxtamembrane extracellular sequences which regulate the ability of TACE (TNFα converting enzyme, ADAM17) to proteolytically cleave ErbB4 from the cell surface. These isoforms exhibit tissue specific expression. Another isoform lacks the phosphoinositide 3kinase activation sequence present in the ErbB4 cytoplasmic domain. Human ErbB4 consists of 1308 amino acids (aa) with a 25 aa signal sequence, a 626 aa extracellular domain, a 24 aa transmembrane region, and a 633 aa cytoplasmic domain. ErbB4 appears to play important roles in neuronal development, development of the heart and cancer.