Publication Date:
2005-09-17
Description:
A small number of mammalian signaling pathways mediate a myriad of distinct physiological responses to diverse cellular stimuli. Temporal control of the signaling module that contains IkappaB kinase (IKK), its substrate inhibitor of NF-kappaB (IkappaB), and the key inflammatory transcription factor NF-kappaB can allow for selective gene activation. We have demonstrated that different inflammatory stimuli induce distinct IKK profiles, and we examined the underlying molecular mechanisms. Although tumor necrosis factor-alpha (TNFalpha)-induced IKK activity was rapidly attenuated by negative feedback, lipopolysaccharide (LPS) signaling and LPS-specific gene expression programs were dependent on a cytokine-mediated positive feedback mechanism. Thus, the distinct biological responses to LPS and TNFalpha depend on signaling pathway-specific mechanisms that regulate the temporal profile of IKK activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Werner, Shannon L -- Barken, Derren -- Hoffmann, Alexander -- GM071573/GM/NIGMS NIH HHS/ -- GM72024/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2005 Sep 16;309(5742):1857-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Signaling Systems Laboratory, Department of Chemistry and Biochemistry, 9500 Gilman Drive, Mailcode 0375, La Jolla, CA 92093-0375, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16166517" target="_blank"〉PubMed〈/a〉
Keywords:
Algorithms
;
Animals
;
Autocrine Communication
;
Cell Line
;
Cells, Cultured
;
Computer Simulation
;
Cytokines/genetics
;
Feedback, Physiological
;
Gene Expression Profiling
;
*Gene Expression Regulation
;
I-kappa B Kinase
;
I-kappa B Proteins/metabolism
;
Lipopolysaccharides/immunology/metabolism/pharmacology
;
Mice
;
Models, Biological
;
NF-kappa B/deficiency/metabolism
;
Oligonucleotide Array Sequence Analysis
;
Protein-Serine-Threonine Kinases/*metabolism
;
Receptors, Immunologic/metabolism
;
Signal Transduction
;
Toll-Like Receptor 4
;
Transcriptional Activation
;
Tumor Necrosis Factor-alpha/deficiency/immunology/metabolism/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
