Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a mediator of multiple physiological and pathological pathways

HB-EGF is found in two forms, the precursor proHB-EGF and its cleaved product, mature HB-EGF. ProHB-EGF plays a vital role in a number of processes such as juxtacrine activation and DT binding. Mature HB-EGF is a potent chemotactic and mitogenic factor. The transition of proHB-EGF to mature HB-EGF is tightly regulated by specific metalloproteinases. This shedding process plays a central role in GPCR-mediated EGFR transactivation. Antagonizing these metalloproteinases can inhibit transactivation of EGFR and may be of therapeutic value, for example, in cardiac hypertrophy. The ectodomain shedding of HB-EGF also give rise in the cytoplasm to HB-EGF-C, which modulates transcriptional regulation of the cell cycle. Recently, HB-EGF deficient mice have revealed the essential role of this factor in heart and lung development. The abnormal phenotypes of mice expressing only mature HB-EGF, and mice expressing only a non-cleavable mutant of HB-EGF have highlighted the importance of having physiological control over the HB-EGF shedding process. Further investigation will focus the uniqueness of HB-EGF among EGF family growth factors in normal development and disease processes. © 2004 Taylor & Francis Ltd.