Epidermal Growth Factor Receptor Overview

Epidermal growth factor receptor (EGF receptor) belongs to the ErbB family of receptor tyrosine kinases (RTK). EGF receptor is cell surface receptor that activated by binding of its specific ligands, including epidermal growth factor and transforming growth factor α (TGFα).

As members of growth factor receptors, EGF receptor plays key roles in essential cellular functions including proliferation and migration. However, its aberrant activity in the pathogenesis of human cancers underlies our need to understand the complex regulation of EGFR activity and downstream signaling events. There're four EGF receptor, namely, HER1, ERBB2, ERBB3 and ERBB4.

EGFR Gene of EGF Receptor

The HER family of four naturally occurring receptors and one tumor-specific mutant can activate signaling via a complex and sophisticated range of mechanisms, which we are only beginning to understand. HER1/EGFR downstream signaling can lead to tumor growth and development via a host of processes, including enhanced cellular proliferation, survival, and metastasis. A range of potential therapeutic targets exists within the HER signaling system, both inside and outside the cell.

ERBB2 Gene of EGF Receptor

This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized.

ERBB3 Gene of EGF Receptor

This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized.

ERBB4 Gene of EGF Receptor

This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.