Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 20 October 2009
Vol. 2, Issue 93, p. ra65
[DOI: 10.1126/scisignal.2000599]

RESEARCH ARTICLES

Editor's Summary

Prolonging NF-{kappa}B Activation
Regulation of the activity of the transcription factor NF-{kappa}B, which plays key roles in immune responses, exhibits complicated cellular dynamics. Tumor necrosis factor–{alpha} (TNF-{alpha}), a proinflammatory cytokine that activates the death-domain receptor TNFR, and lipopolysaccharide (LPS), a pathogen-derived molecule that activates the Toll-like receptor TLR4, both activate NF-{kappa}B. Lee et al. provide a mechanism by which cells respond to these two ligands with different kinetics. Cells responding to TNF-{alpha} exhibit an oscillating translocation of NF-{kappa}B in and out of the nucleus, with all cells responding similarly. In contrast, cells responding to LPS showed two distinct modes, with one population exhibiting transient nuclear localization of NF-{kappa}B and a second exhibiting persistent nuclear localization. Lee et al. modified an existing computational model of the pathways that activate NF-{kappa}B and found that cells responding to LPS produce TNF-{alpha} in concentrations that are low enough that only a subset of neighboring cells responds. This paracrine TNF-{alpha} signal produces the population of LPS-responsive cells with persistent prolonged NF-{kappa}B activation.

Citation: T. K. Lee, E. M. Denny, J. C. Sanghvi, J. E. Gaston, N. D. Maynard, J. J. Hughey, M. W. Covert, A Noisy Paracrine Signal Determines the Cellular NF-{kappa}B Response to Lipopolysaccharide. Sci. Signal. 2, ra65 (2009).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Switching of the Relative Dominance Between Feedback Mechanisms in Lipopolysaccharide-Induced NF-{kappa}B Signaling.
M.-H. Sung, N. Li, Q. Lao, R. A. Gottschalk, G. L. Hager, and I. D. C. Fraser (2014)
Science Signaling 7, ra6
   Abstract »    Full Text »    PDF »
Tunable Signal Processing Through Modular Control of Transcription Factor Translocation.
N. Hao, B. A. Budnik, J. Gunawardena, and E. K. O'Shea (2013)
Science 339, 460-464
   Abstract »    Full Text »    PDF »
TWEAK and cIAP1 Regulate Myoblast Fusion Through the Noncanonical NF-{kappa}B Signaling Pathway.
E. K. Enwere, J. Holbrook, R. Lejmi-Mrad, J. Vineham, K. Timusk, B. Sivaraj, M. Isaac, D. Uehling, R. Al-awar, E. LaCasse, et al. (2012)
Science Signaling 5, ra75
   Abstract »    Full Text »    PDF »
Interrogation of Inhibitor of Nuclear Factor {kappa}B {alpha}/Nuclear Factor {kappa}B (I{kappa}B{alpha}/NF-{kappa}B) Negative Feedback Loop Dynamics: FROM SINGLE CELLS TO LIVE ANIMALS IN VIVO.
B. L. Moss, A. Elhammali, T. Fowlkes, S. Gross, A. Vinjamoori, C. H. Contag, and D. Piwnica-Worms (2012)
J. Biol. Chem. 287, 31359-31370
   Abstract »    Full Text »    PDF »
p53 Dynamics Control Cell Fate.
J. E. Purvis, K. W. Karhohs, C. Mock, E. Batchelor, A. Loewer, and G. Lahav (2012)
Science 336, 1440-1444
   Abstract »    Full Text »    PDF »
Spatiotemporal Inhibition of Innate Immunity Signaling by the Tbc1d23 RAB-GAP.
L. De Arras, I. V. Yang, B. Lackford, D. W. H. Riches, R. Prekeris, J. H. Freedman, D. A. Schwartz, and S. Alper (2012)
J. Immunol. 188, 2905-2913
   Abstract »    Full Text »    PDF »
Akt Fine-tunes NF-{kappa}B-dependent Gene Expression during T Cell Activation.
J. Cheng, B. Phong, D. C. Wilson, R. Hirsch, and L. P. Kane (2011)
J. Biol. Chem. 286, 36076-36085
   Abstract »    Full Text »    PDF »
Physiological levels of TNF{alpha} stimulation induce stochastic dynamics of NF-{kappa}B responses in single living cells.
D. A. Turner, P. Paszek, D. J. Woodcock, D. E. Nelson, C. A. Horton, Y. Wang, D. G. Spiller, D. A. Rand, M. R. H. White, and C. V. Harper (2010)
J. Cell Sci. 123, 2834-2843
   Abstract »    Full Text »    PDF »
Population robustness arising from cellular heterogeneity.
P. Paszek, S. Ryan, L. Ashall, K. Sillitoe, C. V. Harper, D. G. Spiller, D. A. Rand, and M. R. H. White (2010)
PNAS 107, 11644-11649
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 5 January 2010.
M. B. Yaffe and A. M. VanHook (2010)
Science Signaling 3, pc1
   Abstract »    Full Text »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882