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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
44
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pubmed:dateCreated |
1996-12-26
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pubmed:abstractText |
Epidermal growth factor (EGF)-stimulated Ras activation involves specific interactions between the EGF receptor (EGFR), the adaptor proteins Grb2 and Shc, and the nucleotide exchange factor Sos-1. Study and control of these protein-protein interactions in vivo can be greatly promoted by introducing intracellular reagents that mimic EGFR functions. Here, we showed that a synthetic phosphopeptide encompassing the autophosphorylation site 1068 of EGFR formed a complex with endogenous Grb2 after this peptide was delivered into intact cells by a cell-permeable peptide import technique. Consequently, this intracellular peptide inhibited EGF-induced EGFR/Grb2 associations but not EGFR/Shc or Shc/Grb2 associations. Peptide-mediated disruption of the EGF/Grb2/Sos-1 cascade led to reduced Ras activation and mitogen-activated protein kinase activation. These results indicate that the binding of Grb2 to the phosphorylated Tyr-1068 of EGFR is crucial to the EGF-induced Ras/mitogen-activated protein kinase signaling pathway. The application of cell-permeable peptides to this study demonstrates a useful biochemical tool to probe and control various intracellular processes involved in signal transduction and gene transcription.
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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/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Grb2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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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 |
1
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pubmed:volume |
271
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
27456-61
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8910327-3T3 Cells,
pubmed-meshheading:8910327-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:8910327-Amino Acid Sequence,
pubmed-meshheading:8910327-Animals,
pubmed-meshheading:8910327-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:8910327-Cell Membrane Permeability,
pubmed-meshheading:8910327-Epidermal Growth Factor,
pubmed-meshheading:8910327-Fluorescent Antibody Technique, Indirect,
pubmed-meshheading:8910327-GRB2 Adaptor Protein,
pubmed-meshheading:8910327-Humans,
pubmed-meshheading:8910327-Kinetics,
pubmed-meshheading:8910327-Mice,
pubmed-meshheading:8910327-Molecular Sequence Data,
pubmed-meshheading:8910327-Peptide Fragments,
pubmed-meshheading:8910327-Phosphopeptides,
pubmed-meshheading:8910327-Proteins,
pubmed-meshheading:8910327-Receptor, Epidermal Growth Factor,
pubmed-meshheading:8910327-Signal Transduction,
pubmed-meshheading:8910327-Transcription, Genetic,
pubmed-meshheading:8910327-ras Proteins
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pubmed:year |
1996
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pubmed:articleTitle |
Controlling epidermal growth factor (EGF)-stimulated Ras activation in intact cells by a cell-permeable peptide mimicking phosphorylated EGF receptor.
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pubmed:affiliation |
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2363, USA. Liny@ctrvax.vanderbilt.edu
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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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