Evidence for regulation of the tumor necrosis factor α-convertase (TACE) by protein-tyrosine phosphatase PTPH1 Journal Article
| Authors: | Zheng, Y.; Schlondorff, J.; Blobel, C. P. |
| Article Title: | Evidence for regulation of the tumor necrosis factor α-convertase (TACE) by protein-tyrosine phosphatase PTPH1 |
| Abstract: | Tumor necrosis factor α-convertase (TACE) is a metalloprotease-disintegrin involved in the ectodomain shedding of several proteins and is critical for proper murine development. TACE-mediated ectodomain shedding is regulated, and the cytoplasmic domain of TACE contains several potential signaling motifs, suggesting that this domain may play a role in regulating the metalloprotease activity. Here we report that the protein-tyrosine phosphatase PTPH1, which contains both a band 4.1 domain and a single PDZ domain, can interact with the cytoplasmic domain of TACE. The interaction was initially observed in a yeast two-hybrid screen and was confirmed using an in vitro binding assay and co-immunoprecipitations from eukaryotic cell extracts. The interaction is mediated via binding of the PDZ domain of PTPH1 to the COOH terminus of TACE. The latter represents a novel group I PDZ binding sequence characterized by a terminal cysteine residue. In co-expression experiments, significantly lower levels of TACE were observed in the presence of catalytically active forms of PTPH1 compared with catalytically inactive forms of PTPH1. Furthermore, phorbol ester-stimulated shedding of the TACE substrate tumor necrosis factor-α was decreased in cells expressing catalytically active PTPH1 compared with inactive PTPH1. Taken together, these results suggest that PTPH1 may be a negative regulator of TACE levels and function, and thus provide the first evidence for the regulation of TACE through a cytoplasmic protein. |
| Keywords: | controlled study; nonhuman; protein domain; protein motif; proteins; animal cell; animals; amino acid substitution; carboxy terminal sequence; protein protein interaction; in vitro study; enzyme activity; enzyme substrate; cercopithecus aethiops; cos cells; animalia; genetic vectors; transcription factors; cloning, molecular; enzyme regulation; amino acid sequence; kinetics; recombinant fusion proteins; tumors; eukaryota; escherichia coli; immunoprecipitation; murinae; mutagenesis, site-directed; binding sites; protein tyrosine phosphatase; yeast; saccharomyces cerevisiae proteins; catalysis; cysteine; enzyme mechanism; adam proteins; assays; phorbol ester; enzyme active site; cells; binding assay; protein-tyrosine-phosphatase; hybrid; tumor necrosis factor alpha converting enzyme; metalloendopeptidases; humans; priority journal; article; cytoplasmic domains |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 277 |
| Issue: | 45 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2002-11-08 |
| Start Page: | 42463 |
| End Page: | 42470 |
| Language: | English |
| DOI: | 10.1074/jbc.M207459200 |
| PUBMED: | 12207026 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
