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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2002-4-15
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pubmed:abstractText |
We report that the Forkhead family of transcription factors, FKHRL1, FKHR and AFX are novel components of neurotrophin receptor signaling. NGF rapidly induced the phosphorylation of FKHRL1 in PC12 cells. This effect is mediated by high-affinity TrkA receptor as nerve growth factor (NGF) induced the phosphorylation of FKHRL1 only in TrkA expressing cells and not p75-expressing cells. Additional experiments with various kinase inhibitors, the transient expression of constitutively active and dominant-negative Akt, and in vitro kinase assay revealed that phosphatidylinositol-3 (PtdIns3)/Akt kinase mediated the actions of NGF. Similar data were obtained for brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) in primary cortical cultured neurons. These findings demonstrate for the first time that the phosphorylation of the Forkhead family of transcription factors can be modulated by neurotrophins via Trk receptors and PtdIns3K/Akt kinase (but not MAP or S6p70 kinases) in neuronal and non-neuronal cells. Moreover, survival assays with the PtdIns3 kinase inhibitor LY294002, active and dominant-negative forms of Akt indicate that the phosphorylation of FKHRL1 plays a role in neurotrophins-mediated cell survival.
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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/Brain-Derived Neurotrophic Factor,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/FOXO1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/FOXO3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/FOXO4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/FoxO3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Foxo1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Foxo1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Foxo1a protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Foxo3a protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotrophin 3,
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/Receptor, Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, trkA,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/neurotrophin 4
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-3042
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
80
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1049-61
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11953455-3T3 Cells,
pubmed-meshheading:11953455-Active Transport, Cell Nucleus,
pubmed-meshheading:11953455-Animals,
pubmed-meshheading:11953455-Brain-Derived Neurotrophic Factor,
pubmed-meshheading:11953455-Cell Survival,
pubmed-meshheading:11953455-Cells, Cultured,
pubmed-meshheading:11953455-DNA-Binding Proteins,
pubmed-meshheading:11953455-Enzyme Inhibitors,
pubmed-meshheading:11953455-Forkhead Transcription Factors,
pubmed-meshheading:11953455-Humans,
pubmed-meshheading:11953455-Mice,
pubmed-meshheading:11953455-Nerve Growth Factor,
pubmed-meshheading:11953455-Nerve Growth Factors,
pubmed-meshheading:11953455-Nerve Tissue Proteins,
pubmed-meshheading:11953455-Neurons,
pubmed-meshheading:11953455-Neurotrophin 3,
pubmed-meshheading:11953455-PC12 Cells,
pubmed-meshheading:11953455-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11953455-Phosphorylation,
pubmed-meshheading:11953455-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11953455-Proto-Oncogene Proteins,
pubmed-meshheading:11953455-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11953455-Rats,
pubmed-meshheading:11953455-Rats, Sprague-Dawley,
pubmed-meshheading:11953455-Receptor, Nerve Growth Factor,
pubmed-meshheading:11953455-Receptor, trkA,
pubmed-meshheading:11953455-Receptors, Nerve Growth Factor,
pubmed-meshheading:11953455-Signal Transduction,
pubmed-meshheading:11953455-Transcription Factors,
pubmed-meshheading:11953455-Transfection
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pubmed:year |
2002
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pubmed:articleTitle |
FKHRL1 and its homologs are new targets of nerve growth factor Trk receptor signaling.
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pubmed:affiliation |
Douglas Hospital Research Center, Departments of Psychiatry, and Pharmacology and Therapeutics, McGill University, Montreal, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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