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We studied ADAMs 12, 19, and 33 because they are phylogenetically related to an ADAM (Xenopus ADAM13) that functions in Xenopus cranial neural crest migration (Alfandari et al., 2001), and because they are expressed in mouse cranial neural crest (Tomczuk, 2004). We first extended our analysis to ADAM17 (tumor necrosis factor-α converting enzyme), an important ADAM that was recently shown to interact with the α5β1 integrin (Bax et al., 2004). As seen in Figure 5B, both the poorly processed (SGAA) and the protease dead (E/A) mutants inhibited migration as much as wild-type ADAM12. As seen in Figure 6C, E/A ADAM12 was transported to the cell surface and processed as well as wild-type ADAM12. The molecular weights of these ADAM constructs reflect the presence of the 6Xmyc tag appended at the C terminus of each construct. Wild-type and the disintegrin loop (D488A) ADAM12 (A); wild-type ADAM12 and ADAM12 with mutations in the putative furin cleavage sites (B); wild-type and E/A (protease inactive) ADAM12 (C); and wild-type ADAMs 12, 17, 19, and 33 (D).
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