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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5116
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pubmed:dateCreated |
1993-7-26
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pubmed:abstractText |
Insulin-induced activation of extracellular signal-regulated kinases [ERKs, also known as mitogen-activated protein (MAP) kinases] is mediated by Ras. Insulin activates Ras primarily by increasing the rate of guanine nucleotide-releasing activity. Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains. Moreover, a dominant negative form of Ras (with Ser17 substituted with Asn) blocked insulin-induced activation of ERKs in cells that overexpressed GRB2. GRB2 overexpression led to increased formation of a complex between the guanine nucleotide-releasing factor Sos (the product of the mammalian homolog of son of sevenless gene) and GRB2. In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways.
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pubmed:grant |
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
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/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Son of Sevenless Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0036-8075
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
260
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1953-5
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:8316835-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:8316835-Amino Acid Sequence,
pubmed-meshheading:8316835-Animals,
pubmed-meshheading:8316835-Cell Line,
pubmed-meshheading:8316835-Enzyme Activation,
pubmed-meshheading:8316835-Epidermal Growth Factor,
pubmed-meshheading:8316835-GRB2 Adaptor Protein,
pubmed-meshheading:8316835-Insulin,
pubmed-meshheading:8316835-Insulin Receptor Substrate Proteins,
pubmed-meshheading:8316835-Membrane Proteins,
pubmed-meshheading:8316835-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:8316835-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:8316835-Mitogen-Activated Protein Kinases,
pubmed-meshheading:8316835-Molecular Sequence Data,
pubmed-meshheading:8316835-Phosphoproteins,
pubmed-meshheading:8316835-Phosphorylation,
pubmed-meshheading:8316835-Protein-Serine-Threonine Kinases,
pubmed-meshheading:8316835-Proteins,
pubmed-meshheading:8316835-Receptor, Insulin,
pubmed-meshheading:8316835-Signal Transduction,
pubmed-meshheading:8316835-Son of Sevenless Proteins
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pubmed:year |
1993
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pubmed:articleTitle |
The function of GRB2 in linking the insulin receptor to Ras signaling pathways.
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pubmed:affiliation |
Department of Pharmacology, New York University Medical Center, NY 10016.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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