The epidermal growth factor receptor ligands at a glance.
The epidermal growth factor receptor (EGFR) regulates key processes of cell biology, including proliferation, survival, and differentiation during development, tissue homeostasis, and tumorigenesis. Canonical EGFR activation involves the binding of seven peptide growth factors. These ligands are synthesized as transmembrane proteins comprising an N-terminal extension, the EGF module, a short juxtamembrane stalk, a hydrophobic transmembrane domain, and a carboxy-terminal fragment. The central structural and functional feature is the EGF module, a sequence containing six cysteines in a conserved spacement which is responsible for binding to the EGFR. While the membrane-anchored peptide can be biologically active by juxtacrine signaling, in most cases the EGF module is proteolytically cleaved (a process termed ectodomain shedding) to release the soluble growth factor, which may act in an endocrine, paracrine, or autocrine fashion. This review summarizes the structural and functional properties of these fascinating molecules and presents selected examples to illustrate their roles in development, physiology, and pathology.
Schneider
Marlon R
MR
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany. schnder@lmb.uni-muenchen.de
Wolf
Eckhard
E
D000595:Amino Acid Sequence; D000818:Animals; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
D008024:Ligands; D066246:ErbB Receptors