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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2006-8-1
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pubmed:abstractText |
Homologues of signal peptide peptidase (SPPLs) are putative aspartic proteases that may catalyse regulated intramembrane proteolysis of type II membrane-anchored signalling factors. Here, we show that four human SPPLs are each sorted to a different compartment of the secretory pathway. We demonstrate that SPPL2a and SPPL2b, which are sorted to endosomes and the plasma membrane, respectively, are functional proteases that catalyse intramembrane cleavage of tumour necrosis factor alpha (TNFalpha). The two proteases promoted the release of the TNFalpha intracellular domain, which in turn triggers expression of the pro-inflammatory cytokine interleukin-12 by activated human dendritic cells. Our study reveals a critical function for SPPL2a and SPPL2b in the regulation of innate and adaptive immunity.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1465-7392
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
843-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16829952-Animals,
pubmed-meshheading:16829952-Aspartic Acid Endopeptidases,
pubmed-meshheading:16829952-Bacterial Proteins,
pubmed-meshheading:16829952-Blotting, Western,
pubmed-meshheading:16829952-Cell Line,
pubmed-meshheading:16829952-Cell Membrane,
pubmed-meshheading:16829952-Cells, Cultured,
pubmed-meshheading:16829952-Dendritic Cells,
pubmed-meshheading:16829952-Endosomes,
pubmed-meshheading:16829952-Flow Cytometry,
pubmed-meshheading:16829952-HeLa Cells,
pubmed-meshheading:16829952-Humans,
pubmed-meshheading:16829952-Hydrolysis,
pubmed-meshheading:16829952-Interleukin-12,
pubmed-meshheading:16829952-Intracellular Membranes,
pubmed-meshheading:16829952-Isoenzymes,
pubmed-meshheading:16829952-Microscopy, Fluorescence,
pubmed-meshheading:16829952-RNA Interference,
pubmed-meshheading:16829952-Tumor Necrosis Factor-alpha
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pubmed:year |
2006
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pubmed:articleTitle |
SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production.
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pubmed:affiliation |
Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), ETH Hoenggerberg, 8092 Zurich, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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