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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
45
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pubmed:dateCreated |
2002-11-4
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pubmed:abstractText |
Tumor necrosis factor alpha-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-alpha 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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADAM Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GAL4 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/tumor necrosis factor-alpha...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
42463-70
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12207026-ADAM Proteins,
pubmed-meshheading:12207026-Amino Acid Substitution,
pubmed-meshheading:12207026-Animals,
pubmed-meshheading:12207026-Binding Sites,
pubmed-meshheading:12207026-COS Cells,
pubmed-meshheading:12207026-Cercopithecus aethiops,
pubmed-meshheading:12207026-Cloning, Molecular,
pubmed-meshheading:12207026-DNA-Binding Proteins,
pubmed-meshheading:12207026-Escherichia coli,
pubmed-meshheading:12207026-Genetic Vectors,
pubmed-meshheading:12207026-Humans,
pubmed-meshheading:12207026-Kinetics,
pubmed-meshheading:12207026-Metalloendopeptidases,
pubmed-meshheading:12207026-Mutagenesis, Site-Directed,
pubmed-meshheading:12207026-Protein Tyrosine Phosphatase, Non-Receptor Type 3,
pubmed-meshheading:12207026-Protein Tyrosine Phosphatases,
pubmed-meshheading:12207026-Recombinant Fusion Proteins,
pubmed-meshheading:12207026-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:12207026-Transcription Factors
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pubmed:year |
2002
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pubmed:articleTitle |
Evidence for regulation of the tumor necrosis factor alpha-convertase (TACE) by protein-tyrosine phosphatase PTPH1.
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pubmed:affiliation |
Graduate Program in Physiology, Biophysics and Molecular Medicine, Weill Graduate School of Medical Science of Cornell University, New York, New York 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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