EGF receptor ligands: recent advances.

Bhuminder Singh,Graham Carpenter,Robert J Coffey

doi:10.12688/f1000research.9025.1

Abstract

Seven ligands bind to and activate the mammalian epidermal growth factor (EGF) receptor (EGFR/ERBB1/HER1): EGF, transforming growth factor-alpha (TGFA), heparin-binding EGF-like growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), and epigen (EPGN). Of these, EGF, TGFA, HBEGF, and BTC are thought to be high-affinity ligands, whereas AREG, EREG, and EPGN constitute low-affinity ligands. This focused review is meant to highlight recent studies related to actions of the individual EGFR ligands, the interesting biology that has been uncovered, and relevant advances related to ligand interactions with the EGFR.

Highlights

The role of the epidermal growth factor receptor (EGFR) in the generation of biological responses has been reviewed extensively, an analysis of EGFR ligands, crucial initiators of these responses, has not been reviewed recently[1,2,3,4,5,6,7,8]
All EGFR ligands are synthesized as type 1 transmembrane precursors that undergo extracellular domain cleavage to release soluble ligands, which bind to and activate the EGFR
We discuss the ligands individually, we point out that these ligands do not act in isolation but rather affect the behavior of each other to accomplish a diverse repertoire of biological responses through EGFR signaling

Summary

Introduction

The role of the epidermal growth factor receptor (EGFR) in the generation of biological responses has been reviewed extensively, an analysis of EGFR ligands, crucial initiators of these responses, has not been reviewed recently[1,2,3,4,5,6,7,8]. The often observed co-expression of EPGN, EREG, AREG, and BTC, which may be due to their chromosomal clustering on human 4q13-21 and 5E1 in the mouse, further complicates our understanding of the role of individual ligands in biological processes[55]. Recent work in mammalian cells has found at least two novel roles for inactive rhomboids (iRhoms) in the processing of EGFR ligand precursors[73]. Abbreviations ADAM, a disintegrin and metalloprotease; AREG, amphiregulin; BTC, betacellulin; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; EPGN, epigen; ER, endoplasmic reticulum; EREG, epiregulin; ExTRAcrine, exosomal targeted receptor activation; HBEGF, heparin-binding epidermal growth factor-like growth factor; IFN, interferon; IL, interleukin; iRhom, inactive rhomboid; MDCK, Madin-Darby canine kidney; MIF, migration inhibitory factor; miR, microRNA; NKD2, Naked[2]; TGFA, transforming growth factor-alpha. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Cohen S

PubMed Abstract

69. Leahy DJ

73. Freeman M

Findings

87. Pike LJ