Functional analysis of ADAMs (A Disintegrin And Metalloproteinase) and related transmembrane proteases
Metalloprotease-dependent proteolysis on the cell surface is essential for normal cellular functions during development and in the adult, but it may also have undesirable consequences by promoting diseases such as cancer, arthritis, and atherosclerosis. In particularly, the disintegrin-like metalloproteases ADAM10 and ADAM17 are involved in the release of substrates with important roles in development and in disease, including cytokines, growth factors, receptors, adhesion proteins and other proteins such as the amyloid precursor protein. Therefore, it is very likely that dysregulation of these enzymes contributes to the imbalance observed under pathological conditions. However, the mechanisms underlying the regulation of ectodomain shedding are still poorly understood. We would like to gain deeper insights into the regulation of ADAM10 and ADAM17-mediated proteolysis and to increase the understanding about the functional consequences of protein ectodomain shedding.
Reiss and Saftig, Seminars in Cell & Developmental Biology, 2009