ADAM17 and gastrointestinal tract diseases: clinical aspects with translational messages

Vertebrate cells express a number of membrane markers including cytokines, chemokines, growth factors, and inflammatory signaling molecules. These markers go cleaved in a special process named "ectodomain shedding", either to allow response to environmental changes, or to maintain intercellular dialogue. Their extracellular domain may retain specific activity, or can be changed into an inactive decoy molecule, whereas the inner domain translocates to the nucleus and interacts with the genome. This polyvalent cleavage is mediated by a particular protein family, ADAM (A disintegrin and metalloprotease) which acts as "molecular scissor." The human proteome includes at least 22 functionally and structurally different ADAMs. In this review, we focus on ADAM17, a protease with a marked impact on physiologic activities and pathologic functions in the gastrointestinal tract.