Shedding light on ADAM metalloproteinases

: Huovila AP, Turner AJ, Pelto-Huikko M, Kärkkäinen I, Ortiz RM

: 2005

: Trends in Biochemical Sciences

: Trends in biochemical sciences

: Trends Biochem Sci

: 30

: 7

: 413

: 22

: 0968-0004

DOI: https://doi.org/10.1016/j.tibs.2005.05.006

ADAM metalloproteinase disintegrins have emerged as the major proteinase family that mediates ectodomain shedding, the proteolytic release of extracellular domains from their membrane-bound precursors. Recent gene-manipulation studies have established the role of ADAM-mediated shedding in mammalian physiology and, in addition, raised the issue of functional redundancy among ADAM sheddases. ADAM sheddases activate, for example, growth factors and cytokines, thus regulating signalling pathways that are important in development and pathological processes such as cancer. The recent studies have also begun to elucidate the substrate specificity and the mechanisms that control ADAM-mediated shedding events that regulate, for example, growth-factor and Notch signalling, and the processing of the amyloid precursor protein.