Source:http://linkedlifedata.com/resource/pubmed/id/16274239
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
45
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pubmed:dateCreated |
2005-11-8
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pubmed:abstractText |
We have investigated functional effects of glycosylation at N(579) of the epidermal growth factor receptor (EGFR). Our previous study showed that the population of cell-surface expressed EGFRs in A431 cells, a human epidermoid carcinoma cell line, is composed of two subpopulations that differ by glycosylation at N(579) [Zhen et al. (2003) Biochemistry 42, 5478-5492]. To characterize the subpopulation of receptors not glycosylated at N(579), we established a 32D cell line expressing a point mutant of the EGFR (N579Q), which cannot be glycosylated at this position. Analysis of epitope accessibility suggests that the lack of glycosylation at N(579) weakens auto-inhibitory tether interactions, and cross-linking experiments suggest a somewhat elevated level of preformed N579Q-EGFR dimers in the absence of ligand relative to wild-type EGFR (WT-EGFR). However, ligand drives the majority of N579Q-EGFR dimerization, suggesting that untethering, while necessary, is not sufficient to drive dimerization. Ligand-binding experiments reveal a much greater fraction of N579Q-EGFRs in a high-affinity state compared to the fraction of WT-EGFRs in a high-affinity state. However, differences in the kinetic association and dissociation rates indicate that the high-affinity states of the WT and the N579Q receptors are distinct. EGF-stimulated phosphorylation in cells expressing N579Q-EGFRs results in notable differences in the pattern of tyrosine phosphorylated proteins compared with that obtained in cells expressing WT-EGFRs. Moreover, although WT-EGFRs confer cell survival in 32D cells in the absence of interleukin-3 and EGF, we found that receptors lacking glycosylation at N(579) do not. This is the first study of which we are aware to show that selective glycosylation of a specific N-glycosylation site can produce two functionally distinct receptors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Asparagine,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
14920-31
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16274239-Antibodies,
pubmed-meshheading:16274239-Asparagine,
pubmed-meshheading:16274239-Cell Line, Tumor,
pubmed-meshheading:16274239-Cell Proliferation,
pubmed-meshheading:16274239-Cell Survival,
pubmed-meshheading:16274239-Epidermal Growth Factor,
pubmed-meshheading:16274239-Glycosylation,
pubmed-meshheading:16274239-Humans,
pubmed-meshheading:16274239-Kinetics,
pubmed-meshheading:16274239-Ligands,
pubmed-meshheading:16274239-Point Mutation,
pubmed-meshheading:16274239-Protein Conformation,
pubmed-meshheading:16274239-Receptor, Epidermal Growth Factor
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pubmed:year |
2005
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pubmed:articleTitle |
Functional effects of glycosylation at Asn-579 of the epidermal growth factor receptor.
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pubmed:affiliation |
Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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