Heparin-binding epidermal growth factor and Src family kinases in proliferation of renal epithelial cells

摘要

HB-EGF is synthesized as a transmembrane protein (proHB-EGF) and is commonly cleaved at the apical plasma membrane to yield soluble HB-EGF (18, 19, 47). Ectodomain shedding, the proteolytic processing of the extracellular domain of proHB-EGF to form soluble HB-EGF, is observed in response to several stimuli, including 12-0-tetradecanoylphorbol-13-aceate, osmotic stress, and UV light (18, 49). Whereas initial studies of signaling and regulation of HB-EGF ectodomain shedding suggested that matrix metalloproteases -2, -3, and/or -9 were involved in this process (19, 38, 47), recent studies provide strong evidence that tumor necrosis factor-a-converting enzyme/a disintegrin and metalloprotease 17 protease (TACE/ ADAM17) and ADAM10 are involved in HB-EGF shedding (10, 16,41).