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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
1997-12-5
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pubmed:abstractText |
In contrast to two-chain urokinase (uPA), a chemical conjugate between uPA and native saporin (a cytotoxic plant seed ribosome-inactivating protein) did not require plasminogen activator inhibitors to be internalized. To dissect this pathway, we constructed a chimera consisting of the amino-terminal fragment (ATF) of human urokinase fused to a saporin isoform (SAP-3). The chimeric ATF-SAP toxin was expressed in Escherichia coli, purified, and characterized for its ribosome-inactivating activity. Besides being a potent inhibitor of protein synthesis in cell-free assays, ATF-SAP was specifically cytotoxic toward cells expressing human uPAR. Competition experiments indicated that both the human uPAR and the LDL-related receptor protein are involved in mediating the cell killing ability of ATF-SAP. We conclude that neither plasminogen activator inhibitors nor the catalytic moiety of urokinase are necessary to initiate these internalization pathways. Thus, saporin may play a role similar to plasminogen activator inhibitors in its ability to trigger internalization of uPAR-bound ligands through endocytic receptors.
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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/Immunotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/N-Glycosyl Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/PLAUR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Plant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Urokinase Plasminogen...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosome Inactivating Proteins...,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/saporin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0892-6638
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1169-76
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9367352-Cell Line,
pubmed-meshheading:9367352-Cell Survival,
pubmed-meshheading:9367352-Cloning, Molecular,
pubmed-meshheading:9367352-Escherichia coli,
pubmed-meshheading:9367352-Humans,
pubmed-meshheading:9367352-Immunotoxins,
pubmed-meshheading:9367352-N-Glycosyl Hydrolases,
pubmed-meshheading:9367352-Peptide Fragments,
pubmed-meshheading:9367352-Plant Proteins,
pubmed-meshheading:9367352-Protein Synthesis Inhibitors,
pubmed-meshheading:9367352-Receptors, Cell Surface,
pubmed-meshheading:9367352-Receptors, Urokinase Plasminogen Activator,
pubmed-meshheading:9367352-Recombinant Fusion Proteins,
pubmed-meshheading:9367352-Recombinant Proteins,
pubmed-meshheading:9367352-Ribosome Inactivating Proteins, Type 1,
pubmed-meshheading:9367352-Ribosomes,
pubmed-meshheading:9367352-Tumor Cells, Cultured,
pubmed-meshheading:9367352-Urokinase-Type Plasminogen Activator
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pubmed:year |
1997
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pubmed:articleTitle |
The amino-terminal fragment of human urokinase directs a recombinant chimeric toxin to target cells: internalization is toxin mediated.
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pubmed:affiliation |
Dibit-Department of Biological and Technological Research, San Raffaele Scientific Institute, Milano, Italy. fabbris@dibit.hsr.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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