Linked Life Data

16321974

Source:http://linkedlifedata.com/resource/pubmed/id/16321974

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-1-30
pubmed:abstractText
Dynamic properties of signaling pathways control their behavior and function. We undertook an iterative computational and experimental investigation of the dynamic properties of tumor necrosis factor (TNF)alpha-mediated activation of the transcription factor NF-kappaB. Surprisingly, we found that the temporal profile of the NF-kappaB activity is invariant to the TNFalpha dose. We reverse engineered a computational model of the signaling pathway to identify mechanisms that impart this important response characteristic, thus predicting that the IKK activity profile must transiently peak at all TNFalpha doses to generate the observed NF-kappaB dynamics. Experimental confirmation of this prediction emphasizes the importance of mechanisms that rapidly down-regulate IKK following TNFalpha activation. A refined computational model further revealed signaling characteristics that ensure robust TNFalpha-mediated cell-cell communication over considerable distances, allowing for fidelity of cellular inflammatory responses in infected tissue.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2945-50
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Transient IkappaB kinase activity mediates temporal NF-kappaB dynamics in response to a wide range of tumor necrosis factor-alpha doses.
pubmed:affiliation
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural