Oscillatory Phosphorylation of Yeast Fus3 MAP Kinase Controls Periodic Gene Expression and Morphogenesis

Hilioti, Zoe; Sabbagh, Walid; Paliwal, Saurabh; Bergmann, Adriel; Goncalves, Marcus D.; Bardwell, Lee; Levchenko, Andre

doi:10.1016/j.cub.2008.11.024

Cited by 16 publications

(25 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results illustrate that the oscillatory parameter space is quite large and therefore likely to be encountered in vivo. This view is supported by the recent experimental observation of MAPK oscillations (Hilioti et al, 2008;Shankaran et al, 2009).…”

Section: Discussionsupporting

confidence: 56%

Bifurcations and chaos in the MAPK signaling cascade

Zumsande

Groß

2010

Journal of Theoretical Biology

View full text Add to dashboard Cite

The mitogen-activated protein kinase (MAPK) cascade is an important signaling cascade in eukaryotes. We use the approach of generalized modeling to analyze the dynamics of the MAPK cascade and identify key mechanisms of instability. Furthermore, we report sustained multi-mode oscillations and potentially chaotic behavior caused by a sequestration-based feedback mechanism. Finally, we investigate the interplay between sequestration and external feedback loops. Our analysis thereby confirms, extends and generalizes previous results obtained by conventional modeling and points out the diversity of dynamics that sequestration can bring about.

show abstract

Section: Discussionsupporting

confidence: 56%

Bifurcations and chaos in the MAPK signaling cascade

Zumsande

Groß

2010

Journal of Theoretical Biology

View full text Add to dashboard Cite

show abstract

“…A recent study shows that in these cells, oscillations of Fus3 MAPK activity depend on transcriptional induction of the MAPK phosphatase Msg5 and the negative regulator of pheromone receptor signalling, Sst2 (REF. 28). The Fus3 oscillations are observed on the same timescale (2–3 hours) as the periodic formation of additional mating projections28.…”

Section: Temporal Network Dynamics and Cell Fatementioning

confidence: 99%

Signalling ballet in space and time

Kholodenko

Hancock²,

Kölch

2010

Nat Rev Mol Cell Biol

576

570

View full text Add to dashboard Cite

Although we have amassed extensive catalogues of signalling network components, our understanding of the spatiotemporal control of emergent network structures has lagged behind. Dynamic behaviour is starting to be explored throughout the genome, but analysis of spatial behaviours is still confined to individual proteins. The challenge is to reveal how cells integrate temporal and spatial information to determine specific biological functions. Key findings are the discovery of molecular signalling machines such as Ras nanoclusters, spatial activity gradients and flexible network circuitries that involve transcriptional feedback. They reveal design principles of spatiotemporal organization that are crucial for network function and cell fate decisions.

show abstract

“…Fus3-GFP and Fus1-GFP protein levels display strong oscillatory dynamics with frequencies similar to the oscillations of Fus3 activation. Furthermore, increasing the pheromone dose has been observed to result in a progressive phase shift of Fus3-GFP expression peaks towards earlier time points; this trend is also observed for phospho-MAPK levels so that it is now established that the expression levels of MAPK target genes oscillate in approximate synchrony with MAPK activation levels (see Hilioti et al 2008). Likewise, the effect of MAPK cascade oscillations on the hippocampal neuron memory has recently been characterized (see Gerstner et al 2009).…”

Section: Discussionmentioning

confidence: 86%

“…MAPK Fus3 is a key regulator of the yeast mating pheromone response and is known to undergo sustained oscillations in its phosphorylation/activation state during continuous pheromone exposure (see Hilioti et al 2008). The MAPK activity oscillations lead to corresponding oscillations in the mating gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…These oscillations in MAPK activity and gene expression have been empirically observed to need the negative regulator of G-protein signaling Sst2, and partially need the MAPK phosphatase Msg5. The peaks in Fus3 activation are correlated with periodic rounds of cell morphogenesis, with each peak preceding the formation of an additional mating projection (see Hilioti et al 2008). Fus3-GFP and Fus1-GFP protein levels display strong oscillatory dynamics with frequencies similar to the oscillations of Fus3 activation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of robust tunable oscillators using mitogen activated protein kinase cascades

et al. 2010

View full text Add to dashboard Cite

Mitogen activated protein kinase (MAPK) cascade is evolutionally preserved in all eukaryotic cells, and regulates various cellular activities such as gene expression, mitosis, differentiation, and apoptosis. Recently, Bashor et al. have shown that Ste5 scaffold protein can be used to reshape the MAPK cascade through engineered feedback loops, and have used heuristic tuning mechanisms to synthesize the feedback. A problem of interest is to determine whether information regarding the underlying biochemical reactions can be used to synthesize robust feedback that will ensure that the resultant circuit has the desired properties. In this paper, we consider the problem of engineering feedback in MAPK cascade to synthesize an oscillator of the desired frequency. Our approach builds on the MAPK cascade model derived by Chikarmane et al. who have exploited the existence of a Hopf bifurcation point in the Markevich model of the MAPK cascade to synthesize the exciting kinase as a function of the doubly phosphorylated protein. We show how the L 1 -control theory can be used for a robust synthesis of the oscillator and present the simulation results.

show abstract

Oscillatory Phosphorylation of Yeast Fus3 MAP Kinase Controls Periodic Gene Expression and Morphogenesis

Cited by 16 publications

References 0 publications

Bifurcations and chaos in the MAPK signaling cascade

Bifurcations and chaos in the MAPK signaling cascade

Signalling ballet in space and time

Synthesis of robust tunable oscillators using mitogen activated protein kinase cascades

Contact Info

Product

Resources

About