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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6748
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pubmed:dateCreated |
1999-9-27
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pubmed:abstractText |
The mechanisms of cell proliferation and transformation are intrinsically linked to the process of apoptosis: the default of proliferating cells is to die unless specific survival signals are provided. Platelet-derived growth factor (PDGF) is a principal survival factor that inhibits apoptosis and promotes proliferation, but the mechanisms mediating its anti-apoptotic properties are not completely understood. Here we show that the transcription factor NF-kappaB is important in PDGF signalling. NF-kappaB transmits two signals: one is required for the induction of proto-oncogene c-myc and proliferation, and the second, an anti-apoptotic signal, counterbalances c-Myc cytotoxicity. We have traced a putative pathway whereby PDGF activates NF-kappaB through Ras and phospatidylinositol-3-kinase (PI(3)K) to the PKB/Akt protein kinase and the IkappaB kinase (IKK); NF-kappaB thus appears to be a target of the anti-apoptotic Ras/PI(3)K/Akt pathway. We show that, upon PDGF stimulation, Akt transiently associates in vivo with IKK and induces IKK activation. These findings establish a role for NF-kappaB in growth factor signalling and define an anti-apoptotic Ras/PI(3)K/Akt/IKK/NF-kappaB pathway, thus linking anti-apoptotic signalling with transcription machinery.
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pubmed:commentsCorrections |
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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/CHUK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chuk protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ikbkb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ikbke protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
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/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
401
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
86-90
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10485711-3T3 Cells,
pubmed-meshheading:10485711-Animals,
pubmed-meshheading:10485711-Apoptosis,
pubmed-meshheading:10485711-Catalysis,
pubmed-meshheading:10485711-Cell Division,
pubmed-meshheading:10485711-Cells, Cultured,
pubmed-meshheading:10485711-DNA,
pubmed-meshheading:10485711-Gene Expression Regulation,
pubmed-meshheading:10485711-Humans,
pubmed-meshheading:10485711-I-kappa B Kinase,
pubmed-meshheading:10485711-Mice,
pubmed-meshheading:10485711-Mitogens,
pubmed-meshheading:10485711-Mutation,
pubmed-meshheading:10485711-NF-kappa B,
pubmed-meshheading:10485711-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10485711-Platelet-Derived Growth Factor,
pubmed-meshheading:10485711-Protein Binding,
pubmed-meshheading:10485711-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10485711-Proto-Oncogene Proteins,
pubmed-meshheading:10485711-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:10485711-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:10485711-Rats,
pubmed-meshheading:10485711-Recombinant Proteins,
pubmed-meshheading:10485711-Signal Transduction,
pubmed-meshheading:10485711-Transfection,
pubmed-meshheading:10485711-ras Proteins
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pubmed:year |
1999
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pubmed:articleTitle |
NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling.
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pubmed:affiliation |
Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, 27599-7280, 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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