| First Author | Werner SL | Year | 2005 |
| Journal | Science | Volume | 309 |
| Issue | 5742 | Pages | 1857-61 |
| PubMed ID | 16166517 | Mgi Jnum | J:100897 |
| Mgi Id | MGI:3589953 | Doi | 10.1126/science.1113319 |
| Citation | Werner SL, et al. (2005) Stimulus specificity of gene expression programs determined by temporal control of IKK activity. Science 309(5742):1857-61 |
| abstractText | 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. |
