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We next assessed whether other ADAM family members can selectively inhibit integrin-mediated cell migration. Our results so far indicate that ADAM12 inhibits α4β1 integrin-mediated cell migration in transwell and scratch wound assays. The D488A mutant therefore likely has a reduced effect on α4β1-mediated cell migration (Figure 5B) because its disintegrin domain has a reduced affinity for α4β1 integrin (Figure 5A).
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A higher expression level (4 μg per 6-cm dish) of ADAM33 inhibited α5β1-mediated cell migration, but its effect on α4β1-mediated migration was diminished (Huang, Bridges, and White, unpublished data). (B) Scratch wound assays were repeated as in panel A, except that α5-mediated cell migration was scored on the CCBD region of FN. Thus, strikingly, ADAM12 and ADAM17 demonstrate reciprocal effects on α4β1 and α5β1 mediated cell migration (Figure 8, A and B).
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