Fig. 1. Several Drosophila ADAM metalloproteases cleave Delta and Serrate in S2 cells. (A) Phylogenetic tree of ADAM metalloproteases. Drosophila in bold, Anopheles in gray, C. elegans in italics and human underlined. The different human ADAMs have distinct homologs in each of the species. Note that ADAM10 has two homologs in Drosophila (Kuz and Kul) and in Anopheles. Similarly, Meltrin- has two homologs in insects. (B) Kuz and Kul have all the signature domains of ADAM metalloproteases. In the protease and disintegrin domains, Kul shows a higher degree of similarity to the human ADAM10. (C) Dl or Ser were expressed in S2 cells, and their capacity to serve as substrates for co-expressed Drosophila ADAM metalloproteases monitored by the appearance of ligand in the medium, and the concomitant disappearance from the cells. Kul, Kuz and DTACE displayed potent cleavage of both ligands. DMeltrin induced only low levels of Ser cleavage. The activity of the Mmd Meltrin homolog was not examined, because its expression is restricted to the central nervous system (Chase et al., 1987).