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Vinod PK, et al.  (2008) Integration of Global Signaling Pathways, cAMP-PKA, MAPK and TOR in the Regulation of FLO11. PLoS ONE 3(2):e1663

Abstract: The budding yeast, Saccharomyces cerevisiae, responds to various environmental cues by invoking specific adaptive mechanisms for their survival. Under nitrogen limitation, S. cerevisiae undergoes a dimorphic filamentous transition called pseudohyphae, which helps the cell to forage for nutrients and reach an environment conducive for growth. This transition is governed by a complex network of signaling pathways, namely cAMP-PKA, MAPK and TOR, which controls the transcriptional activation of FLO11, a flocculin gene that encodes a cell wall protein. However, little is known about how these pathways co-ordinate to govern the conversion of nutritional availability into gene expression. Here, we have analyzed an integrative network comprised of cAMP-PKA, MAPK and TOR pathways with respect to the availability of nitrogen source using experimental and steady state modeling approach. Our experiments demonstrate that the steady state expression of FLO11 was bistable over a range of inducing ammonium sulphate concentration based on the preculturing condition. We also show that yeast switched from FLO11 expression to accumulation of trehalose, a STRE response controlled by a transcriptional activator Msn2/4, with decrease in the inducing concentration to complete starvation. Steady state analysis of the integrative network revealed the relationship between the environment, signaling cascades and the expression of FLO11. We demonstrate that the double negative feedback loop in TOR pathway can elicit a bistable response, to differentiate between vegetative growth, filamentous growth and STRE response. Negative feedback on TOR pathway function to restrict the expression of FLO11 under nitrogen starved condition and also with re-addition of nitrogen to starved cells. In general, we show that these global signaling pathways respond with specific sensitivity to regulate the expression of FLO11 under nitrogen limitation. The holistic steady state modeling approach of the integrative network revealed how the global signaling pathways could differentiate between multiple phenotypes.

Status: Published Type: Journal Article PubMed ID: 18301741

Topics addressed in this paper

Number of different genes curated to this paper: 14

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
CDC25 CLB2 CLN1 CLN2 FLO11 GPA2 MEP2 MSN2 MSN4 PPH21
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Topics Genes linked to topics (#11 - 14 )
PPH22 RAS2 TOR1 TOR2
Additional Literature blue ball blue ball blue ball blue ball
Cell Growth and Metabolism blue ball blue ball blue ball blue ball
Computational analysis blue ball blue ball blue ball blue ball

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