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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0115305,
umls-concept:C0185117,
umls-concept:C0248813,
umls-concept:C0521447,
umls-concept:C1120843,
umls-concept:C1456820,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1879547,
umls-concept:C2911684
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pubmed:issue |
5
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pubmed:dateCreated |
1997-3-13
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pubmed:abstractText |
E-selectin expression by endothelium is crucial for leukocyte recruitment during inflammatory responses. Transcriptional regulation of the E-selectin promoter by tumor necrosis factor alpha (TNFalpha) requires multiple nuclear factor-kappaB (NF-kappaB) binding sites and a cAMP-responsive element/activating transcription factor-like binding site designated positive domain II (PDII). Here we characterize the role of the stress-activated family of mitogen-activated protein (MAP) kinases in induced expression of this adhesion molecule. By UV cross-linking and immunoprecipitation, we demonstrated that a heterodimer of transcription factors ATF-2 and c-JUN is constitutively bound to the PDII site. TNFalpha stimulation of endothelial cells induces transient phosphorylation of both ATF-2 and c-JUN and induces marked activation of the c-JUN N-terminal kinase (JNK1) and p38 but not extracellular signal-regulated kinase (ERK1). JNK and p38 are constitutively present in the nucleus, and DNA-bound c-JUN and ATF-2 are stably contacted by JNK and p38, respectively. MAP/ERK kinase kinase 1 (MEKK1), an upstream activator of MAP kinases, increases E-selectin promoter transcription and requires an intact PDII site for maximal induction. MEKK1 can also activate NF-kappaB -dependent gene expression. The effects of dominant interfering forms of the JNK/p38 signaling pathway demonstrate that activation of these kinases is critical for cytokine-induced E-selectin gene expression. Thus, TNFalpha activates two signaling pathways, NF-kappaB and JNK/p38, which are both required for maximal expression of E-selectin.
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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/ATF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Activating Transcription Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Probes,
http://linkedlifedata.com/resource/pubmed/chemical/E-Selectin,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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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 |
31
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pubmed:volume |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2753-61
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9006914-Activating Transcription Factor 2,
pubmed-meshheading:9006914-Base Sequence,
pubmed-meshheading:9006914-Binding Sites,
pubmed-meshheading:9006914-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9006914-Cell Nucleus,
pubmed-meshheading:9006914-Cells, Cultured,
pubmed-meshheading:9006914-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:9006914-DNA Primers,
pubmed-meshheading:9006914-DNA Probes,
pubmed-meshheading:9006914-Dimerization,
pubmed-meshheading:9006914-E-Selectin,
pubmed-meshheading:9006914-Endothelium, Vascular,
pubmed-meshheading:9006914-Humans,
pubmed-meshheading:9006914-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:9006914-Kinetics,
pubmed-meshheading:9006914-Mitogen-Activated Protein Kinases,
pubmed-meshheading:9006914-Models, Biological,
pubmed-meshheading:9006914-NF-kappa B,
pubmed-meshheading:9006914-Promoter Regions, Genetic,
pubmed-meshheading:9006914-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:9006914-Signal Transduction,
pubmed-meshheading:9006914-Transcription, Genetic,
pubmed-meshheading:9006914-Transcription Factors,
pubmed-meshheading:9006914-Tumor Necrosis Factor-alpha,
pubmed-meshheading:9006914-Umbilical Veins,
pubmed-meshheading:9006914-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
1997
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pubmed:articleTitle |
Tumor necrosis factor alpha-induced E-selectin expression is activated by the nuclear factor-kappaB and c-JUN N-terminal kinase/p38 mitogen-activated protein kinase pathways.
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pubmed:affiliation |
Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, 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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