Metalloproteinase-Mediated Shedding of Heparin-Binding Egf-Like Growth Factor and Its Pathophysiological Roles

Heparin-binding EGF-like growth factor (HB-EGF) exists as a membrane-anchored form (proHBEGF) and as its soluble cleaved product (sHB-EGF). The conversion (ectodomain shedding) of proHB-EGF to sHB-EGF is tightly regulated by specific metalloproteinases. Ectodomain shedding plays a central role in GPCR-mediated EGFR transactivation. Antagonizing metalloproteinases can inhibit EGFR transactivation and might be of therapeutic value, for example in cardiac hypertrophy, skin remodeling and tumor growth.