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rdf:type |
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lifeskim:mentions |
umls-concept:C0015309,
umls-concept:C0018270,
umls-concept:C0040549,
umls-concept:C0162768,
umls-concept:C0314768,
umls-concept:C0392760,
umls-concept:C0678594,
umls-concept:C1323367,
umls-concept:C1510411,
umls-concept:C1514562,
umls-concept:C1521761,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
7
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pubmed:dateCreated |
1989-10-13
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pubmed:abstractText |
TGF-alpha-PE40 is a hybrid protein composed of transforming growth factor-alpha (TGF-alpha) fused to a 40,000-dalton segment of Pseudomonas exotoxin A (PE40). This hybrid protein possesses the receptor-binding activity of TGF-alpha and the cell-killing properties of PE40. These properties enable TGF-alpha-PE40 to bind to and kill tumor cells that possess epidermal growth factor (EGF) receptors. Unexpectedly, TGF-alpha-PE40 binds approximately 100-fold less effectively to EGF receptors than does native TGF-alpha (receptor-binding inhibition IC50 = 540 and 5.5 nM, respectively). To understand the factors governing receptor binding, deletions and site-specific substitutions were introduced into the PE40 domain of TGF-alpha-PE40. Removal of the N-terminal 59 or 130 amino acids from the PE40 domain of TGF-alpha-PE40 improved receptor binding (IC50 = 340 and 180 nM, respectively) but decreased cell-killing activity. Substitution of alanines for cysteines at positions 265 and 287 within the PE40 domain dramatically improved receptor binding (IC50 = 37 nM) but also decreased cell-killing activity. Similar substitutions of alanines for cysteines at positions 372 and 379 within the PE40 domain did not significantly affect receptor-binding or cell-killing activities. These studies indicate that the PE40 domain of TGF-alpha-PE40 interferes with EGF receptor binding. The cysteine residues at positions 265 and 287 of PE40 are responsible for a major part of this interference.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-1105573,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-166383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-19354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-265521,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-2710128,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-271968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-2850475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-2981413,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-2999006,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3006045,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3095831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3098436,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3131768,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3132465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3283735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3299371,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3477813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3501577,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3531211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-3855503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-388439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-4357758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-5432063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-6201861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-6269464,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-6276390,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-6312838,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-6320373,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-6606682,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2779550-6811955
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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/ADP Ribose Transferases,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Exotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors,
http://linkedlifedata.com/resource/pubmed/chemical/toxA protein, Pseudomonas aeruginosa
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0270-7306
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2860-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:2779550-ADP Ribose Transferases,
pubmed-meshheading:2779550-Bacterial Toxins,
pubmed-meshheading:2779550-Cell Line, Transformed,
pubmed-meshheading:2779550-Cloning, Molecular,
pubmed-meshheading:2779550-Cysteine,
pubmed-meshheading:2779550-DNA,
pubmed-meshheading:2779550-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:2779550-Exotoxins,
pubmed-meshheading:2779550-Humans,
pubmed-meshheading:2779550-Mutation,
pubmed-meshheading:2779550-Plasmids,
pubmed-meshheading:2779550-Receptor, Epidermal Growth Factor,
pubmed-meshheading:2779550-Recombinant Fusion Proteins,
pubmed-meshheading:2779550-Recombinant Proteins,
pubmed-meshheading:2779550-Transforming Growth Factors,
pubmed-meshheading:2779550-Virulence Factors
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pubmed:year |
1989
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pubmed:articleTitle |
Epidermal growth factor receptor binding is affected by structural determinants in the toxin domain of transforming growth factor-alpha-Pseudomonas exotoxin fusion proteins.
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pubmed:affiliation |
Department of Cancer Research, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
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pubmed:publicationType |
Journal Article
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