Proteolytic release of membrane bound intercellular regulators

The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha (TNF alpha) is released. Analyses of cells lacking t his metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell surface proteins, including a TNF receptor, the L -selectin adhesion molecule, and transforming growth factor-alpha (TGF alph a). The phenotype of mice lacking TACE suggests an essential role for solub le TGF alpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.