An essential role for ectodomain shedding in mammalian development |
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Authors: | JJ Peschon JL Slack P Reddy KL Stocking SW Sunnarborg DC Lee WE Russell BJ Castner RS Johnson JN Fitzner RW Boyce N Nelson CJ Kozlosky MF Wolfson CT Rauch DP Cerretti RJ Paxton CJ March RA Black |
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Affiliation: | Immunex Corporation, Seattle, WA 98101, USA. peschon@immunex.com |
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Abstract: | The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha) 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-alpha (TGFalpha). The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo. |
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