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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5549
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pubmed:dateCreated |
2001-12-13
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pubmed:abstractText |
ErbB-4 is a transmembrane receptor tyrosine kinase that regulates cell proliferation and differentiation. After binding of its ligand heregulin (HRG) or activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA), the ErbB-4 ectodomain is cleaved by a metalloprotease. We now report a subsequent cleavage by gamma-secretase that releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus. gamma-Secretase cleavage was prevented by chemical inhibitors or a dominant negative presenilin. Inhibition of gamma-secretase also prevented growth inhibition by HRG. gamma-Secretase cleavage of ErbB-4 may represent another mechanism for receptor tyrosine kinase-mediated signaling.
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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/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/BACE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bace1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Carbamates,
http://linkedlifedata.com/resource/pubmed/chemical/Dipeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Unsaturated,
http://linkedlifedata.com/resource/pubmed/chemical/L 685458,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Neuregulin-1,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/leptomycin B,
http://linkedlifedata.com/resource/pubmed/chemical/receptor tyrosine-protein kinase...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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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 |
7
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pubmed:volume |
294
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2179-81
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:11679632-Active Transport, Cell Nucleus,
pubmed-meshheading:11679632-Amino Acid Sequence,
pubmed-meshheading:11679632-Amyloid Precursor Protein Secretases,
pubmed-meshheading:11679632-Animals,
pubmed-meshheading:11679632-Aspartic Acid Endopeptidases,
pubmed-meshheading:11679632-COS Cells,
pubmed-meshheading:11679632-Carbamates,
pubmed-meshheading:11679632-Cell Division,
pubmed-meshheading:11679632-Cell Line,
pubmed-meshheading:11679632-Cell Membrane,
pubmed-meshheading:11679632-Cell Nucleus,
pubmed-meshheading:11679632-Cytoplasm,
pubmed-meshheading:11679632-Dipeptides,
pubmed-meshheading:11679632-Endopeptidases,
pubmed-meshheading:11679632-Fatty Acids, Unsaturated,
pubmed-meshheading:11679632-Humans,
pubmed-meshheading:11679632-Membrane Proteins,
pubmed-meshheading:11679632-Metalloendopeptidases,
pubmed-meshheading:11679632-Mice,
pubmed-meshheading:11679632-Molecular Sequence Data,
pubmed-meshheading:11679632-Mutation,
pubmed-meshheading:11679632-Neuregulin-1,
pubmed-meshheading:11679632-Presenilin-1,
pubmed-meshheading:11679632-Protease Inhibitors,
pubmed-meshheading:11679632-Protein Structure, Tertiary,
pubmed-meshheading:11679632-Receptor, Epidermal Growth Factor,
pubmed-meshheading:11679632-Recombinant Fusion Proteins,
pubmed-meshheading:11679632-Signal Transduction,
pubmed-meshheading:11679632-Tetradecanoylphorbol Acetate,
pubmed-meshheading:11679632-Transcriptional Activation,
pubmed-meshheading:11679632-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
gamma -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase.
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pubmed:affiliation |
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
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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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