Source:http://linkedlifedata.com/resource/pubmed/id/11133986
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2001-5-25
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pubmed:abstractText |
Signal transduction by the antigen receptor complexes is critical for developmental progression of B-lymphocytes, which are defined by assembly and sequential expression of immunoglobulin genes, which in turn are regulated by the enhancer elements. Although proximal antigen-receptor signal transduction pathways are well defined, the precise nuclear factors targeted by these signals remained unknown. Previous studies have demonstrated that tissue-restricted transcription factors including PU.1 and PU.1 interaction partner (PIP) function synergistically with c-Fos plus c-Jun to stimulate the kappaE3'-enhancer in 3T3 cells. In this study, we demonstrate that the functional synergy between these factors is enhanced in response to mitogen-activated protein kinase kinase kinase, in 3T3 cells, where the enhancer is inactive. However in S194 plasmacytoma cells, mitogen-activated protein kinase kinase kinase was able to stimulate the activity of PU.1 but unable to induce the kappaE3'-enhancer activity. We have found that Ras-phosphoinositide 3-kinase-dependent externally regulated kinase, AKT, induces kappaE3'-enhancer activity in both pre-B and plasmacytoma cells. AKT stimulation of the kappaE3'-enhancer is primarily due to PU.1 induction and is independent of PU.1 interaction with PIP. Activation of AKT had no effect on the expression levels of PU.1 or its protein-protein interaction with PIP. Using a series of deletion constructs, we have determined that the PU.1 acid-rich (amino acids 33-74) transactivation domain is necessary for AKT-mediated induction. Substitution analyses within this region indicate that phosphorylation of Ser(41) is necessary to respond to AKT. Consistent with these studies, ligation of antigen receptors in A20 B cells mimics AKT activation of PU.1. Taken together, these results provide evidence that PU.1 is induced by AKT signal in a phosphoinositide 3-kinase-dependent manner, leading to inducible or constitutive activation of its target genes.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Map3k1 protein, mouse,
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/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, B-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/interferon regulatory factor-4,
http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein Spi-1
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8460-8
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:11133986-3T3 Cells,
pubmed-meshheading:11133986-Animals,
pubmed-meshheading:11133986-DNA,
pubmed-meshheading:11133986-DNA-Binding Proteins,
pubmed-meshheading:11133986-Enhancer Elements, Genetic,
pubmed-meshheading:11133986-Interferon Regulatory Factors,
pubmed-meshheading:11133986-MAP Kinase Kinase Kinase 1,
pubmed-meshheading:11133986-Mice,
pubmed-meshheading:11133986-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11133986-Phosphorylation,
pubmed-meshheading:11133986-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11133986-Proto-Oncogene Proteins,
pubmed-meshheading:11133986-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11133986-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:11133986-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:11133986-Receptors, Antigen, B-Cell,
pubmed-meshheading:11133986-Trans-Activators,
pubmed-meshheading:11133986-Transcription, Genetic,
pubmed-meshheading:11133986-Transcriptional Activation
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pubmed:year |
2001
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pubmed:articleTitle |
AKT induces transcriptional activity of PU.1 through phosphorylation-mediated modifications within its transactivation domain.
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pubmed:affiliation |
Department of Biochemistry, MCP Hahnemann University School of Medicine, Philadelphia, Pennsylvania 19102, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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