Fig. 3. Structure-function analysis of Kul. The activity of Kul was monitored in S2 cells, by its capacity to release Dl to the medium and reduce the levels of the protein in the cells. Following expression of Dl alone, some cleavage can be detected, presumably by endogenous ADAM proteins. The levels of cleaved Dl are markedly elevated following co-expression of full-length Kul. A mutation leading to the elimination of the catalytic activity (Kul E-A), removal of the cytoplasmic tail (Kul Ex), or inactivating the cleavage site of the pro-domain (Pro-Kul), abolished the capacity of Kul to cleave Dl. Furthermore, in all three cases the activity of the endogenous ADAMs was also compromised.