ErbB Receptors: Directing key signaling networks throughout life

• Published in: Annual review of pharmacology and toxicology Vol. 44; no. 1; pp. 195 - 217
• Main Authors: HOLBRO, Thomas, HYNES, Nancy E
• Format: Journal Article
• Language: English
• Published: Palo Alto, CA Annual Reviews 01-01-2004; Annual Reviews, Inc
• Subjects: Aging - metabolism; Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Clinical Trials as Topic; General aspects; Humans; Medical sciences; Mutation; Neoplasms - drug therapy; Neoplasms - metabolism; Pharmacology. Drug treatments; Receptor, Epidermal Growth Factor - drug effects; Receptor, Epidermal Growth Factor - metabolism; Receptor, Epidermal Growth Factor - physiology; Receptor, ErbB-2 - metabolism; Receptor, ErbB-2 - physiology; Receptor, ErbB-3 - metabolism; Receptor, ErbB-3 - physiology; Receptor, ErbB-4; Signal Transduction - physiology; Human; Ligand; Cytokine; Rodentia; Malignant tumor; Vertebrata; Mammalia; Epidermal growth factor; Treatment; Mouse; Signaling pathway; Polypeptide; Animal; Growth factor; Biological receptor
• ISSN: 0362-1642; 1545-4304
• DOI: 10.1146/annurev.pharmtox.44.101802.121440

The epidermal growth factor (EGF)-related peptides bind the ErbB receptors, inducing the formation of different homo- and heterodimers. Receptor dimerization promotes activation of the intrinsic kinase, leading to phosphorylation of specific tyrosines located in the ErbB's cytoplasmic region. These phosphorylated residues serve as docking sites for a variety of signaling molecules whose recruitment stimulates intracellular signaling cascades, which ultimately control diverse genetic programs. Particular ligand-receptor complexes have essential roles in embryonic development as well as in the adult. Finally, ErbB receptors are being pursued as therapeutic targets because aberrant ErbB activity has been observed in many human cancers. In this review, we discuss these data in more detail, illustrating the importance of tightly regulated ErbB signaling throughout life.