ADAMs and ADAMTSs

Abstract

Proteolysis has emerged as a key post-translational regulator of the function of molecules on the cell surface and in the extracellular milieu. In principle, proteolysis can activate or inactivate a substrate, or can change its functional properties. ADAMs (a disintegrin and metalloprotease) and ADAMTS (a disintegrin-like and metalloprotease domain with thrombospondin type 1 repeats) proteases are related members of a superfamily of metallo-endopeptidases that also includes MMPs and astacins. ADAMs are integral membrane proteins that typically cleave other membrane anchored proteins, whereas ADAMTS proteases lack a membrane anchor, and process both cell-surface and secreted molecules, the latter mostly extracellular matrix (ECM) components. ADAMs are implicated in fertilization, neurogenesis, in regulating the function of ligands for the EGF-receptor, and in the release of proteins such as the pro-inflammatory cytokine TNFα from the plasma membrane. ADAMTS proteases have key roles in embryonic development, including lung development, the molecular maturation of von Willebrand factor and procollagen as well as organization of fibrillin microfibrils in ECM, and are implicated in the pathogenesis of diverse lung and airway disorders. Here, we provide a general overview of the biochemical properties and physiological functions of ADAMs and ADAMTS proteases and describe their relevance to lung and airway disorders.