%0 Journal Article
%T Inhibitory role of TACE/ADAM17 cytotail in protein ectodomain shedding
%A Xiaojin Li
%A Liliana P¨¦rez
%A Huizhou Fan
%J World Journal of Biological Chemistry
%D 2011
%I Baishideng Publishing Group Co. Limited
%R 10.4331/wjbc.v2.i11.246
%X AIM: To determine if the cytotail of the principal sheddase tumor necrosis factor-¦Á converting enzyme (TACE; ADAM17) controls protein ectodomain shedding. METHODS: Site-directed mutagenesis was performed to derive TACE variants. The resulting TACE expression plasmids with amino acid substitutions in the extracellular, cysteine-rich disintegrin domain (CRD) and/or deleted cytotail, along with an expression vector for the enhanced green fluorescence protein were transfected into shedding-defective M1 mutants stably expressing transmembrane L-selectin or transforming growth factor (TGF)-¦Á. The expression levels of the TACE substrates at the cell surface were determined by flow cytometry. RESULTS: Consistent with published data, a single point mutation (C600Y) in the CRD led to shedding deficiency. However, removal of the cytotail from the C600Y TACE variant partially restored ectodomain cleavage of TGF-¦Á and L-selectin. Cytotail-deleted mutants with any other substituting amino acid residues in place of Cys600 displayed similar function compared with tail-less C600Y TACE. CONCLUSION: The cytotail plays an inhibitory role, which becomes evident when it is removed from an enzyme with another mutation that affects the enzyme function.
%K ADAM17
%K Ectodomain shedding
%K L-selectin
%K Tumor necrosis factor-¦Á converting enzyme
%U http://www.wjgnet.com/1949-8454/full/v2/i11/246.htm