Error message

No crossref credentials set for sci

Feedback Loops Shape Cellular Signals in Space and Time

Science, 17 October 2008
Vol. 322, Issue 5900, p. 390-395
DOI: 10.1126/science.1160617

Feedback Loops Shape Cellular Signals in Space and Time

  1. Onn Brandman1,
  2. Tobias Meyer2
  1. 1 Department of Cellular and Molecular Pharmacology, University of California-San Francisco and Howard Hughes Medical Institute, San Francisco, CA 94158, USA. E-mail: Onn.Brandman{at}
  2. 2 Department of Chemical and Systems Biology, 318 Campus Drive, Clark Building W200, Stanford University Medical Center, Stanford, CA 94305–5174, USA. E-mail: tobias1{at}


Positive and negative feedback loops are common regulatory elements in biological signaling systems. We discuss core feedback motifs that have distinct roles in shaping signaling responses in space and time. We also discuss approaches to experimentally investigate feedback loops in signaling systems.


O. Brandman and T. Meyer, Feedback Loops Shape Cellular Signals in Space and Time. Science 322, 390-395 (2008).

Shigella flexneri Regulation of ARF6 Activation during Bacterial Entry via an IpgD-Mediated Positive Feedback Loop
A. C. Garza-Mayers, K. A. Miller, B. C. Russo, D. V. Nagda, and M. B. Goldberg
mBio 6, e02584-14-e02584-14 (1 May 2015)

Endogenous Cholinergic Input to the Pontine REM Sleep Generator Is Not Required for REM Sleep to Occur
K. P. Grace, L. E. Vanstone, and R. L. Horner
J. Neurosci. 34, 14198-14209 (22 October 2014)

UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity
Z. Wang, L. M. Linden, K. M. Naegeli, J. W. Ziel, Q. Chi, E. J. Hagedorn, N. S. Savage, and D. R. Sherwood
JCB 206, 619-633 (1 September 2014)

BioFNet: biological functional network database for analysis and synthesis of biological systems
H. Kurata, K. Maeda, T. Onaka, and T. Takata
Brief Bioinform 15, 699-709 (1 September 2014)

EFA6 controls Arf1 and Arf6 activation through a negative feedback loop
D. Padovani, M. Folly-Klan, A. Labarde, S. Boulakirba, V. Campanacci, M. Franco, M. Zeghouf, and J. Cherfils
Proc. Natl. Acad. Sci. USA 111, 12378-12383 (26 August 2014)

The hidden switches underlying ROR{alpha}-mediated circuits that critically regulate uncontrolled cell proliferation
D. Shin, I. S. Kim, J. M. Lee, S.-Y. Shin, J.-H. Lee, S. H. Baek, and K.-H. Cho
J Mol Cell Biol 6, 338-348 (1 August 2014)

Theoretical and experimental analysis links isoform- specific ERK signalling to cell fate decisions
M. Schilling, T. Maiwald, S. Hengl, D. Winter, C. Kreutz, W. Kolch, W. D. Lehmann, J. Timmer, and U. Klingmuller
Mol Syst Biol 5, 334-334 (28 July 2014)

Prediction and validation of a mechanism to control the threshold for inhibitory synaptic plasticity
Y. Kitagawa, T. Hirano, and S.-y. Kawaguchi
Mol Syst Biol 5, 280-280 (28 July 2014)

Unraveling the regulatory connections between two controllers of breast cancer cell fate
J. Lee, A. Tiwari, V. Shum, G. B. Mills, M. A. Mancini, O. A. Igoshin, and G. Balazsi
Nucleic Acids Res 42, 6839-6849 (17 June 2014)

Phosphorylation-dependent derepression by the response regulator HnoC in the Shewanella oneidensis nitric oxide signaling network
L. Plate, and M. A. Marletta
Proc. Natl. Acad. Sci. USA 110, E4648-E4657 (26 November 2013)

srGAP1 regulates lamellipodial dynamics and cell migratory behavior by modulating Rac1 activity
D. Yamazaki, T. Itoh, H. Miki, and T. Takenawa
Mol. Biol. Cell 24, 3393-3405 (1 November 2013)

Gprk2 adjusts Fog signaling to organize cell movements in Drosophila gastrulation
N. Fuse, F. Yu, and S. Hirose
Development 140, 4246-4255 (15 October 2013)

Ultrasensitive response motifs: basic amplifiers in molecular signalling networks
Q. Zhang, S. Bhattacharya, and M. E. Andersen
Open Biol 3, 130031-130031 (24 April 2013)

Avalanche-like behavior in ciliary import
W. B. Ludington, K. A. Wemmer, K. F. Lechtreck, G. B. Witman, and W. F. Marshall
Proc. Natl. Acad. Sci. USA 110, 3925-3930 (5 March 2013)

Calcium oscillations-coupled conversion of actin travelling waves to standing oscillations
M. Wu, X. Wu, and P. De Camilli
Proc. Natl. Acad. Sci. USA 110, 1339-1344 (22 January 2013)

Synergistic dual positive feedback loops established by molecular sequestration generate robust bimodal response
O. S. Venturelli, H. El-Samad, and R. M. Murray
Proc. Natl. Acad. Sci. USA 109, E3324-E3333 (27 November 2012)

Bottom-up construction of in vitro switchable memories
A. Padirac, T. Fujii, and Y. Rondelez
Proc. Natl. Acad. Sci. USA 109, E3212-E3220 (20 November 2012)

Understanding cancer mechanisms through network dynamics
T. M. K. Cheng, S. Gulati, R. Agius, and P. A. Bates
Briefings in Functional Genomics 11, 543-560 (1 November 2012)

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
J Biol Chem 287, 31359-31370 (7 September 2012)

SCAR knockouts in Dictyostelium: WASP assumes SCAR's position and upstream regulators in pseudopods
D. M. Veltman, J. S. King, L. M. Machesky, and R. H. Insall
JCB 198, 501-508 (20 August 2012)

Regulation of oscillation dynamics in biochemical systems with dual negative feedback loops
L. K. Nguyen, J. S. King, L. M. Machesky, and R. H. Insall
J R Soc Interface 9, 1998-2010 (7 August 2012)

Reverse engineering biomolecular systems using -omic data: challenges, progress and opportunities
C. F. Quo, C. Kaddi, J. H. Phan, A. Zollanvari, M. Xu, M. D. Wang, and G. Alterovitz
Brief Bioinform 13, 430-445 (1 July 2012)

The fission yeast septation initiation network (SIN) kinase, Sid2, is required for SIN asymmetry and regulates the SIN scaffold, Cdc11
A. Feoktistova, J. Morrell-Falvey, J.-S. Chen, N. S. Singh, M. K. Balasubramanian, and K. L. Gould
Mol. Biol. Cell 23, 1636-1645 (1 May 2012)

Negative feedback confers mutational robustness in yeast transcription factor regulation
C. M. Denby, J. H. Im, R. C. Yu, C. G. Pesce, and R. B. Brem
Proc. Natl. Acad. Sci. USA 109, 3874-3878 (6 March 2012)

Integrin {alpha}6{beta}4 cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated RhoA activation
K. L. O'Connor, M. Chen, and L. N. Towers
Am. J. Physiol. Cell Physiol. 302, C605-C614 (1 February 2012)

On Fate and Flexibility in Stomatal Development
D. L. Wengier, and D. C. Bergmann
Cold Spring Harb Symp Quant Biol 77, 53-62 (1 January 2012)

Rac regulates PtdInsP3 signaling and the chemotactic compass through a redox-mediated feedback loop
J. W. P. Kuiper, C. Sun, M. A. O. Magalhaes, and M. Glogauer
Blood 118, 6164-6171 (1 December 2011)

Chemotactic cell trapping in controlled alternating gradient fields
B. Meier, A. Zielinski, C. Weber, D. Arcizet, S. Youssef, T. Franosch, J. O. Radler, and D. Heinrich
Proc. Natl. Acad. Sci. USA 108, 11417-11422 (12 July 2011)

Regulation of epidermal growth factor receptor signalling by inducible feedback inhibitors
O. Segatto, S. Anastasi, and S. Alema
J. Cell Sci. 124, 1785-1793 (1 June 2011)

Polarized notum Activation at Wounds Inhibits Wnt Function to Promote Planarian Head Regeneration
C. P. Petersen, and P. W. Reddien
Science 332, 852-855 (13 May 2011)

Kinetic Studies of the Arf Activator Arno on Model Membranes in the Presence of Arf Effectors Suggest Control by a Positive Feedback Loop
D. Stalder, H. Barelli, R. Gautier, E. Macia, C. L. Jackson, and B. Antonny
J Biol Chem 286, 3873-3883 (4 February 2011)

Hindbrain patterning requires fine-tuning of early krox20 transcription by Sprouty 4
C. Labalette, Y. X. Bouchoucha, M. A. Wassef, P. A. Gongal, J. Le Men, T. Becker, P. Gilardi-Hebenstreit, and P. Charnay
Development 138, 317-326 (15 January 2011)

Evolutionary design principles and functional characteristics based on kingdom-specific network motifs
T.-H. Kim, J. Kim, P. Heslop-Harrison, and K.-H. Cho
Bioinformatics 27, 245-251 (15 January 2011)

Context, Specificity, and Self-Organization in Auxin Response
M. Del Bianco, and S. Kepinski
Cold Spring Harb. Perspect. Biol. 3, a001578-a001578 (1 January 2011)

A Conceptual Molecular Network for Chemotactic Behaviors Characterized by Feedback of Molecules Cycling Between the Membrane and the Cytosol
M. Otsuji, Y. Terashima, S. Ishihara, S. Kuroda, and K. Matsushima
Sci Signal 3, ra89-ra89 (14 December 2010)

Systematic Quantification of Negative Feedback Mechanisms in the Extracellular Signal-regulated Kinase (ERK) Signaling Network
M. Cirit, C.-C. Wang, and J. M. Haugh
J Biol Chem 285, 36736-36744 (19 November 2010)

Beyond the wiring diagram: signalling through complex neuromodulator networks
V. Brezina, C.-C. Wang, and J. M. Haugh
Phil Trans R Soc B 365, 2363-2374 (12 August 2010)

Different Roles of G Protein Subunits {beta}1 and {beta}2 in Neutrophil Function Revealed by Gene Expression Silencing in Primary Mouse Neutrophils
Y. Zhang, W. Tang, M. C. Jones, W. Xu, S. Halene, and D. Wu
J Biol Chem 285, 24805-24814 (6 August 2010)

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
Proc. Natl. Acad. Sci. USA 107, 11644-11649 (22 June 2010)

Involvement of the Cytoskeleton in Controlling Leading-Edge Function during Chemotaxis
S. Lee, Z. Shen, D. N. Robinson, S. Briggs, and R. A. Firtel
Mol. Biol. Cell 21, 1810-1824 (1 June 2010)

Signalling complexes and clusters: functional advantages and methodological hurdles
M. Cebecauer, M. Spitaler, A. Serge, and A. I. Magee
J. Cell Sci. 123, 309-320 (1 February 2010)

Adaptive response by state-dependent inactivation
T. Friedlander, and N. Brenner
Proc. Natl. Acad. Sci. USA 106, 22558-22563 (29 December 2009)

Feedback Inhibition of Ammonium Uptake by a Phospho-Dependent Allosteric Mechanism in Arabidopsis
V. Lanquar, D. Loque, F. Hormann, L. Yuan, A. Bohner, W. R. Engelsberger, S. Lalonde, W. X. Schulze, N. von Wiren, W. B. Frommer et al.
Plant Cell 21, 3610-3622 (1 November 2009)

Phosphorylation of Nephrin Triggers Ca2+ Signaling by Recruitment and Activation of Phospholipase C-{gamma}1
Y. Harita, H. Kurihara, H. Kosako, T. Tezuka, T. Sekine, T. Igarashi, I. Ohsawa, S. Ohta, and S. Hattori
J Biol Chem 284, 8951-8962 (27 March 2009)

Ca2+-Calmodulin Feedback Mediates Sensory Adaptation and Inhibits Pheromone-Sensitive Ion Channels in the Vomeronasal Organ
J. Spehr, S. Hagendorf, J. Weiss, M. Spehr, T. Leinders-Zufall, and F. Zufall
J. Neurosci. 29, 2125-2135 (18 February 2009)

From Signals to Patterns: Space, Time, and Mathematics in Developmental Biology
J. Lewis, S. Hagendorf, J. Weiss, M. Spehr, T. Leinders-Zufall, and F. Zufall
Science 322, 399-403 (17 October 2008)

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