Research Article

An Essential Role for Ectodomain Shedding in Mammalian Development

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Science  13 Nov 1998:
Vol. 282, Issue 5392, pp. 1281-1284
DOI: 10.1126/science.282.5392.1281

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The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-α converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-α (TNFα) is released. Analyses of cells lacking this 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-α (TGFα). The phenotype of mice lacking TACE suggests an essential role for soluble TGFα in normal development and emphasizes the importance of protein ectodomain shedding in vivo.

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