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Tumor necrosis factor‐α converting enzyme (TACE or ADAM17) is a member of the ADAM (a disintegrin and metalloproteinase) family of type I membrane proteins and mediates the ectodomain shedding of various membrane‐anchored signaling and adhesion proteins. TACE is synthesized as an inactive zymogen, which is subsequently proteolytically processed to the catalytically active form. We have identified the proprotein‐convertases PC7 and furin to be involved in maturation of TACE. This maturation is negatively influenced by the phorbol ester phorbol‐12‐myristate‐13‐acetate (PMA), which decreases the cellular amount of the mature form of TACE in PMA‐treated HEK293 and SH‐SY5Y cells. Furthermore, we found that stimulation of protein kinase C or protein kinase A signaling pathways did not influence long‐term degradation of mature TACE. Interestingly, PMA treatment of furin‐deficient LoVo cells …