EGF

Epidermal growth factor (EGF) is a small signaling protein that promotes cell growth, proliferation, and differentiation, primarily in epithelial tissues. It exerts its effects by binding to the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, initiating intracellular signaling that supports cell survival and division. In humans, the mature EGF peptide consists of about 53 amino acids, and many tissues can produce a membrane-anchored precursor that is cleaved to release the active form.

EGF was identified in 1962 by Stanley Cohen from extracts of mouse submandibular glands, leading to the concept of growth factors. The discovery, along with Rita Levi-Montalcini’s broader work on growth factors, contributed to Nobel Prize recognition in 1986 for discoveries of growth factors and their receptors. EGF-like domains are also found in a variety of other proteins, reflecting a conserved mechanism of receptor activation.

EGF signals through the EGFR (ErbB1) receptor, and upon ligand binding, the receptor undergoes autophosphorylation and activates downstream pathways such as MAPK/ERK, PI3K/AKT, and JAK/STAT. These cascades regulate transcription, cell cycle progression, and metabolism, influencing processes from normal development to tissue repair.

Physiological roles include involvement in embryonic development, skin and mucosal maintenance, and wound healing. Clinically, dysregulation of the EGFR axis is linked to several cancers, making EGFR and its signaling components targets for therapy. Inhibitors—small-molecule tyrosine kinase inhibitors and monoclonal antibodies—are used to treat various EGFR-driven tumors, reflecting the pathway’s significance in health and disease. EGF also serves as a tool in cell culture to promote epithelial cell growth.