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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
51
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pubmed:dateCreated |
2002-12-16
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pubmed:abstractText |
Reelin is a large secreted protein that controls cortical layering by signaling through the very low density lipoprotein receptor and apolipoprotein E receptor 2, thereby inducing tyrosine phosphorylation of the adaptor protein Disabled-1 (Dab1) and suppressing tau phosphorylation in vivo. Here we show that binding of Reelin to these receptors stimulates phosphatidylinositol 3-kinase, resulting in activation of protein kinase B and inhibition of glycogen synthase kinase 3beta. We present genetic evidence that this cascade is dependent on apolipoprotein E receptor 2, very low density lipoprotein receptor, and Dab1. Reelin-signaling components are enriched in axonal growth cones, where tyrosine phosphorylation of Dab1 is increased in response to Reelin. These findings suggest that Reelin-mediated phosphatidylinositol 3-kinase signaling in neuronal growth cones contributes to final neuron positioning in the mammalian brain by local modulation of protein kinase B and glycogen synthase kinase 3beta kinase activities.
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pubmed:grant |
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pubmed:keyword |
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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, human,
http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules, Neuronal,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-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/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta,
http://linkedlifedata.com/resource/pubmed/chemical/reelin protein
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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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 |
20
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
49958-64
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:12376533-Animals,
pubmed-meshheading:12376533-Brain,
pubmed-meshheading:12376533-Cell Adhesion Molecules, Neuronal,
pubmed-meshheading:12376533-Cell Line,
pubmed-meshheading:12376533-Enzyme Inhibitors,
pubmed-meshheading:12376533-Extracellular Matrix Proteins,
pubmed-meshheading:12376533-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:12376533-Glycogen Synthase Kinase 3,
pubmed-meshheading:12376533-Homozygote,
pubmed-meshheading:12376533-Humans,
pubmed-meshheading:12376533-Immunoblotting,
pubmed-meshheading:12376533-Immunohistochemistry,
pubmed-meshheading:12376533-Mice,
pubmed-meshheading:12376533-Mice, Inbred C57BL,
pubmed-meshheading:12376533-Models, Biological,
pubmed-meshheading:12376533-Nerve Tissue Proteins,
pubmed-meshheading:12376533-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12376533-Phosphorylation,
pubmed-meshheading:12376533-Precipitin Tests,
pubmed-meshheading:12376533-Protein Binding,
pubmed-meshheading:12376533-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12376533-Proto-Oncogene Proteins,
pubmed-meshheading:12376533-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12376533-Rats,
pubmed-meshheading:12376533-Recombinant Proteins,
pubmed-meshheading:12376533-Serine,
pubmed-meshheading:12376533-Serine Endopeptidases,
pubmed-meshheading:12376533-Signal Transduction,
pubmed-meshheading:12376533-Subcellular Fractions,
pubmed-meshheading:12376533-Threonine,
pubmed-meshheading:12376533-Transfection
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pubmed:year |
2002
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pubmed:articleTitle |
Reelin-mediated signaling locally regulates protein kinase B/Akt and glycogen synthase kinase 3beta.
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pubmed:affiliation |
Department of Molecular Genetics, Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, 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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