Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease

Abstract

The epidermal growth factor receptor (EGFR) is the prototypical member of a family of membrane-associated intrinsic tyrosine kinase receptors, the ErbB family. EGFR is activated by multiple ligands, including EGF, transforming growth factor (TGF)-α, HB-EGF, betacellulin, amphiregulin, epiregulin, and epigen. EGFR is expressed in multiple organs and plays important roles in proliferation, survival, and differentiation in both development and normal physiology, as well as in pathophysiological conditions. In addition, EGFR transactivation underlies some important biologic consequences in response to many G protein-coupled receptor (GPCR) agonists. Aberrant EGFR activation is a significant factor in development and progression of multiple cancers, which has led to development of mechanism-based therapies with specific receptor antibodies and tyrosine kinase inhibitors. This review highlights the current knowledge about mechanisms and roles of EGFR in physiology and disease.

Epidermal growth factor prevents APOE4 and amyloid-beta-induced cognitive and cerebrovascular deficits in female mice

“…As EGF did not change Aβ levels, one hypothesis is that EGF acts directly on brain endothelial cells to prevent disrupted signaling induced by the interactive effects of female sex, APOE4 and Aβ in E4FADF mice. This is consistent with our in vitro data [31], the beneficial effect of EGF in wound healing, the promotion of angiogenesis in cancers that produce high EGF levels or that contain a mutation in erbb2 (a dimerization receptor partner of the EGFR), the protective effect of EGF-induced angiogenesis in stroke models and the general protective function of EGF in epithelial tissue (reviewed in [16]). Further, during the course of treatment EGF may have prevented a loss of key proteins involved in the homeostatic functions of brain endothelial cells, prior to vessel degeneration.…”

Genome-scale comparative analysis for host resistance against sea lice between Atlantic salmon and rainbow trout

“…Genes related to the cytoskeleton were identified, such as epidermal growth factor (EGF), found on Ssa9 . This gene is part of a superfamily of receptors with tyrosine kinase activity that have been described in a variety of organs with growth promoter functions, cellular differentiation 46 and could participate in tissue repair by promoting cell growth 36 . In rainbow trout, fibroblast growth factors ( fgf11 - Omy10, fgf13 - Omy29 ) have similar functions (angiogenesis and pro-inflammatory response), and were identified as important genes involved in sea lice resistance by Skugor et al (2009) and Robledo et al (2018) in Atlantic salmon 26,43…”

Deletion of the EGF receptor in vascular smooth muscle cells prevents chronic angiotensin II‐induced arterial wall stiffening and media thickening

“…In cultured cells, it has been shown that an ADAM metalloproteinase domain 17‐ or a cSrc‐mediated epidermal growth factor receptor (EGFR) transactivation can occur . In the case of ADAM, EGFR is activated by shedding and binding of, for example HB‐EGF, deriving from the same or neighbouring cells whereas cSrc leads to direct EGFR phosphorylation . Subsequently, various signalling pathways are activated mediating pathophysiological contributions of EGFR, like vascular dysfunction and fibrosis …”