Epidermal growth factor (EGF) is a small 6 kD polypeptide and has six conserved cysteine residues that form three intramolecular disulfide bonds. Human and mouse EGF share 70% homology in amino acid structure. Mouse EGF is synthesized as a transmembrane precursor protein (1217 amino acids) which is proteolytically cleaved to generate the 53 amino acid mature EGF. Many different cells including mammary gland cells, macrophages, gut epithelial cells, and cells in the nervous system and the kidney can produce EGF. EGF plays important roles in the regulation of cell survival, proliferation, and differentiation by binding to its receptor EGFR. For example, EGF can stimulate the proliferation of mouse embryonic stem cells or induce the terminal differentiation/growth inhibition of A431 cells. The binding of EGF to EGFR will induce receptor dimerization, which is required for activating the tyrosine kinase in the receptor cytoplasmic domain. In addition, the binding of EGF to its receptor triggers several signal transduction pathways including JAK/STAT, Ras/ERK, and PI3K/AKT pathways. Blocking of the EGF/EGFR pathway can suppress some tumor cell's proliferation. Other members of the EGF family (including transforming growth factor-α (TGF-α), heparin-binding EGF-like growth factor (HB-EGF), amphiregulin (AR), betacellulin (BTC), epiregulin (EPR), and epigen also bind to EGFR.