AN ESSENTIAL ROLE FOR ECTODOMAIN SHEDDING IN MAMMALIAN DEVELOPMENT

The ectodomains of numerous proteins are released from cells by proteo lysis to yield soluble intercellular regulators. The responsible prote ase, tumor necrosis factor-a converting enzyme (TACE), has been identi fied only in the case when tumor necrosis factor-alpha (TNF alpha) is released. Analyses of cells lacking this metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell su rface proteins, including a TNF receptor, the L-selectin adhesion mole cule, and transforming growth factor-alpha (TGF alpha). The phenotype of mice Lacking TACE suggests an essential role for soluble TGF alpha in normal development and emphasizes the importance of protein ectodom ain shedding in vivo.