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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
37
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pubmed:dateCreated |
2003-9-8
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pubmed:abstractText |
We hypothesized that glucose-mediated alterations in vascular smooth muscle cell signal transduction contribute to diabetic complications. We found enhanced AngII activation of Akt and extracellular ERK1/2 in vascular smooth muscle cells incubated with high glucose (27.5 mM) compared with low glucose (5.5 mM). Because AngII-mediated transactivation of the epidermal growth factor receptor (EGFR) is important in Akt and ERK1/2 activation, we studied the effects of glucose on EGFR function. The EGFR in cells cultured for 48 h in low glucose was smaller (145 kDa) than the EGFR in cells cultured with high glucose (170 kDa). The shift from the 170-kDa isoform to the 145-kDa isoform was reversible and dependent upon glucose concentration with EC50 approximately 1 mM. N-Glycosylation was responsible because peptide N-glycosidase F treatment of isolated 170-kDa EGFR yielded a single band at 145 kDa. Cell surface biotinylation showed that the 145-kDa EGFR was present on plasma membrane. AngII and other G-protein-coupled receptor ligands known to transactivate EGFR phosphorylated the 170-kDa EGFR but not the 145-kDa EGFR, whereas EGF, heparin-binding EGF-like growth factor, and transforming growth factor-alpha phosphorylated both receptors. Subcellular fractionation showed that the 145-kDa receptor localized to a different plasma membrane domain than the 170-kDa receptor. These results establish a novel mechanism by which glucose-dependent EGFR N-glycosylation modulates AngII signal transduction and suggest a potential mechanism for pathogenic effects of AngII in diabetic vasculopathy.
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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/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35049-56
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12829718-Angiotensin II,
pubmed-meshheading:12829718-Animals,
pubmed-meshheading:12829718-Aorta, Thoracic,
pubmed-meshheading:12829718-Glucose,
pubmed-meshheading:12829718-Glycosylation,
pubmed-meshheading:12829718-Kinetics,
pubmed-meshheading:12829718-Male,
pubmed-meshheading:12829718-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:12829718-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:12829718-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12829718-Models, Biological,
pubmed-meshheading:12829718-Molecular Weight,
pubmed-meshheading:12829718-Muscle, Smooth, Vascular,
pubmed-meshheading:12829718-Phosphorylation,
pubmed-meshheading:12829718-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12829718-Proto-Oncogene Proteins,
pubmed-meshheading:12829718-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12829718-Rats,
pubmed-meshheading:12829718-Rats, Sprague-Dawley,
pubmed-meshheading:12829718-Receptor, Epidermal Growth Factor,
pubmed-meshheading:12829718-Transcriptional Activation
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pubmed:year |
2003
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pubmed:articleTitle |
Epidermal growth factor receptor transactivation is regulated by glucose in vascular smooth muscle cells.
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pubmed:affiliation |
Center for Cardiovascular Research, University of Rochester, Rochester, New York 14642, USA.
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pubmed:publicationType |
Journal Article
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