Amphiregulin (AREG) is a ligand of the epidermal growth factor receptor (EGFR), a widely expressed transmembrane tyrosine kinase. AREG is synthesized as a membrane-anchored precursor protein that can engage in juxtacrine signaling on adjacent cells. Alternatively, after proteolytic processing by cell membrane proteases, mainly TACE/ADAM17, AREG is secreted and behaves as an autocrine or paracrine factor.
AREG gene expression and release is induced by a plethora of stimuli including inflammatory lipids, cytokines, hormones, growth factors and xenobiotics. Through EGFR binding, AREG activates major intracellular signaling cascades governing cell survival, proliferation, and motility. Physiologically, AREG plays an important role in the development and maturation of mammary glands, bone tissue, and oocytes. Chronic elevation of AREG expression is increasingly associated with different pathological conditions, mostly of inflammatory and/or neoplastic nature.
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