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rdf:type |
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lifeskim:mentions |
umls-concept:C0015272,
umls-concept:C0034802,
umls-concept:C0037083,
umls-concept:C0205349,
umls-concept:C0205419,
umls-concept:C0332307,
umls-concept:C1149299,
umls-concept:C1167322,
umls-concept:C1336620,
umls-concept:C1710082,
umls-concept:C2752508
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pubmed:issue |
21
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pubmed:dateCreated |
1994-11-10
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pubmed:abstractText |
Epidermal growth factor (EGF) and type alpha transforming growth factor (TGF-alpha) bind to a specific region in subdomain III of the extracellular portion of the EGF receptor (EGFR). Binding leads to receptor dimerization, auto-and transphosphorylation on intracellular tyrosine residues, and activation of signal transduction pathways. We compared the binding and biological actions of EGF and TGF-alpha in Chinese hamster ovary (CHO) cells expressing either wild-type human EGFR (HER497R) or a variant EGFR that has an arginine-to-lysine substitution in the extracellular domain at codon 497 (HER497K) within subdomain IV of EGFR. Both receptors exhibited two orders of binding sites with radioiodinated EGF (125I-EGF). Similar results were obtained with 125I-TGF-alpha in cells expressing HER497R. In contrast, only one order of low-affinity binding sites was seen with 125I-TGF-alpha in the case of HER497K. Although EGF and TGF-alpha enhanced tyrosine phosphorylation of both receptors, CHO cells expressing HER497K exhibited an attenuated growth response to EGF and TGF-alpha and a reduced induction of the protooncogenes FOS, JUN, and MYC. Moreover, high concentrations of TGF-alpha (5 nM) inhibited growth in these cells but not in cells expressing HER497R. These findings indicate that a region in subdomain IV of EGFR regulates signal transduction across the cell membrane and selectively modulates that binding characteristics of TGF-alpha.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-1326293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-1401070,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-1691502,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-1933884,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-2030916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-2083199,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-2111548,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-2342466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-2553265,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-2788651,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-2790004,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-2832409,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-3260004,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-3260329,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-3494473,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-3497258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-3497713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-3670292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-518835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-6254391,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-6328312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-7506413,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-8114701,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-8313880,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7937865-8466482
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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 |
Oct
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
91
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10217-21
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7937865-Animals,
pubmed-meshheading:7937865-Arginine,
pubmed-meshheading:7937865-Binding Sites,
pubmed-meshheading:7937865-Blotting, Northern,
pubmed-meshheading:7937865-CHO Cells,
pubmed-meshheading:7937865-Cell Division,
pubmed-meshheading:7937865-Cloning, Molecular,
pubmed-meshheading:7937865-Codon,
pubmed-meshheading:7937865-Cricetinae,
pubmed-meshheading:7937865-DNA,
pubmed-meshheading:7937865-Epidermal Growth Factor,
pubmed-meshheading:7937865-Gene Expression,
pubmed-meshheading:7937865-Genes, fos,
pubmed-meshheading:7937865-Genes, jun,
pubmed-meshheading:7937865-Genes, myc,
pubmed-meshheading:7937865-Genetic Variation,
pubmed-meshheading:7937865-Humans,
pubmed-meshheading:7937865-Kinetics,
pubmed-meshheading:7937865-Lysine,
pubmed-meshheading:7937865-Mice,
pubmed-meshheading:7937865-Phosphorylation,
pubmed-meshheading:7937865-Point Mutation,
pubmed-meshheading:7937865-Receptor, Epidermal Growth Factor,
pubmed-meshheading:7937865-Recombinant Proteins,
pubmed-meshheading:7937865-Signal Transduction,
pubmed-meshheading:7937865-Transfection,
pubmed-meshheading:7937865-Transforming Growth Factor alpha
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pubmed:year |
1994
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pubmed:articleTitle |
A variant epidermal growth factor receptor exhibits altered type alpha transforming growth factor binding and transmembrane signaling.
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pubmed:affiliation |
Department of Medicine, University of California, Irvine 92717.
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pubmed:publicationType |
Journal Article
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