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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1997-2-18
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pubmed:abstractText |
Insulin-like growth factor-I (IGF-I) improves glucose metabolism and growth in patients with leprechaunism. We investigated signal transduction through IGF-I receptor in comparison with epidermal growth factor (EGF) receptor in early passages of cultured skin fibroblasts from a normal subject and a patient with leprechaunism whose insulin receptor tyrosine kinase was almost nonexistent. Insulin receptor substrate-1 (IRS-1) became tyrosine-phosphorylated and bound growth factor receptor-bound protein 2 (GRB2) quickly by IGF-I. The association of Shc with GRB2 by IGF-I was detected by immunoblot with anti-Shc antibody but was hardly visible with antiphosphotyrosine antibody, which was in marked contrast to efficient tyrosine phosphorylation of Shc by EGF. However, the potency of IGF-I for DNA synthesis was far stronger than EGF, which was not parallel with the potency of these growth factors to activate Shc or MAP kinase. Rather, phosphatidylinositol (PI) 3-kinase activity, which was activated by IGF-I about 5- to 10-fold more strongly than EGF, appeared to correlate with mitogenesis. Signal transduction pathways following IGF-I receptor or EGF receptor activation were indistinguishable between the normal subject and the patient. Our results strongly suggest that in human skin fibroblasts, which represent a more physiological cell culture: 1) IRS-1, rather than Shc, is the major tyrosine-phosphorylated protein binding GRB2 in initial phase of IGF-I signaling; 2) mitogenic potency of receptor tyrosine kinases such as IGF-I receptor and EGF receptor may not be determined solely by the amount of Shc-GRB2 complex or the activity of MAP kinase; and 3) in contrast to previous reports, IGF-I and EGF receptor signalings are not defective in leprechaunism.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Vesicular...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/SHC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Shc Signaling Adaptor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0013-7227
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
138
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
741-50
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9003010-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:9003010-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:9003010-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9003010-Cell Division,
pubmed-meshheading:9003010-Cells, Cultured,
pubmed-meshheading:9003010-Enzyme Activation,
pubmed-meshheading:9003010-Epidermal Growth Factor,
pubmed-meshheading:9003010-Fibroblast Growth Factor 2,
pubmed-meshheading:9003010-Fibroblasts,
pubmed-meshheading:9003010-Humans,
pubmed-meshheading:9003010-Immunosorbent Techniques,
pubmed-meshheading:9003010-Insulin Receptor Substrate Proteins,
pubmed-meshheading:9003010-Insulin-Like Growth Factor I,
pubmed-meshheading:9003010-Mitogens,
pubmed-meshheading:9003010-Mutation,
pubmed-meshheading:9003010-Phosphoproteins,
pubmed-meshheading:9003010-Phosphorylation,
pubmed-meshheading:9003010-Phosphotyrosine,
pubmed-meshheading:9003010-Proteins,
pubmed-meshheading:9003010-Receptor, IGF Type 1,
pubmed-meshheading:9003010-Receptor, Insulin,
pubmed-meshheading:9003010-Shc Signaling Adaptor Proteins,
pubmed-meshheading:9003010-Signal Transduction
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pubmed:year |
1997
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pubmed:articleTitle |
Roles of insulin receptor substrate-1 and Shc on insulin-like growth factor I receptor signaling in early passages of cultured human fibroblasts.
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pubmed:affiliation |
Institute for Diabetes Care and Research, Asahi Life Foundation, Tokyo, Japan.
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pubmed:publicationType |
Journal Article
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