Dissecting phosphorylation networks: lessons learned from yeast

Mok, Janine; Zhu, Xiaowei; Snyder, M

doi:10.1586/epr.11.64

Cited by 15 publications

(10 citation statements)

References 62 publications

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“…We infer the hierarchical structure of the yeast phosphorylome by using the HSM algorithm. This network is mainly based on protein chip experiments and contains 200 phosphorylation interactions among 94 different kinases [ 11 , 29 ]. Again, for easy comparison we specify the number of hierarchical levels L = 3, which results in 38 top-level, 33 middle-level, and 23 bottom-level kinases (Additional file 2 : Table S2).…”

Section: Resultsmentioning

confidence: 99%

An approach for determining and measuring network hierarchy applied to comparing the phosphorylome and the regulome

et al. 2015

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Many biological networks naturally form a hierarchy with a preponderance of downward information flow. In this study, we define a score to quantify the degree of hierarchy in a network and develop a simulated-annealing algorithm to maximize the hierarchical score globally over a network. We apply our algorithm to determine the hierarchical structure of the phosphorylome in detail and investigate the correlation between its hierarchy and kinase properties. We also compare it to the regulatory network, finding that the phosphorylome is more hierarchical than the regulome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0624-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

An approach for determining and measuring network hierarchy applied to comparing the phosphorylome and the regulome

et al. 2015

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“…MAPK signaling cascades have been well characterized in yeasts (13–16). In filamentous fungi, their function was mainly assigned to pheromone responses and filamentous growth, osmotic stress, and cell wall integrity.…”

Section: Introductionmentioning

confidence: 99%

Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in Aspergillus fumigatus

Manfiolli

Siqueira

Reis

et al. 2019

mBio

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The pathogenic fungus Aspergillus fumigatus is able to adapt to extremely variable environmental conditions. The A. fumigatus genome contains four genes coding for mitogen-activated protein kinases (MAPKs), which are important regulatory knots involved in diverse cellular responses. From a clinical perspective, MAPK activity has been connected to salvage pathways, which can determine the failure of effective treatment of invasive mycoses using antifungal drugs. Here, we report the characterization of the Saccharomyces cerevisiae Fus3 ortholog in A. fumigatus, designated MpkB. We demonstrate that MpkB is important for conidiation and that its deletion induces a copious increase of dihydroxynaphthalene (DHN)-melanin production. Simultaneous deletion of mpkB and mpkA, the latter related to maintenance of the cell wall integrity, normalized DHN-melanin production. Localization studies revealed that MpkB translocates into the nuclei when A. fumigatus germlings are exposed to caspofungin stress, and this is dependent on the cross-talk interaction with MpkA. Additionally, DHN-melanin formation was also increased after deletion of genes coding for the Gα protein GpaA and for the G protein-coupled receptor GprM. Yeast two-hybrid and coimmunoprecipitation assays confirmed that GpaA and GprM interact, suggesting their role in the MpkB signaling cascade. IMPORTANCE Aspergillus fumigatus is the most important airborne human pathogenic fungus, causing thousands of deaths per year. Its lethality is due to late and often inaccurate diagnosis and the lack of efficient therapeutics. The failure of efficient prophylaxis and therapy is based on the ability of this pathogen to activate numerous salvage pathways that are capable of overcoming the different drug-derived stresses. A major role in the protection of A. fumigatus is played by melanins. Melanins are cell wall-associated macromolecules classified as virulence determinants. The understanding of the various signaling pathways acting in this organism can be used to elucidate the mechanism beyond melanin production and help to identify ideal drug targets.

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“…This difficulty is primarily due to the abundance of eukaryotic protein kinases and their multiple and overlapping targets, with hundreds of protein kinases that phosphorylate >50% of the proteome, often at multiple sites within a single protein (Johnson and Hunter, 2005; Sopko and Andrews, 2008; Mok et al ., 2011; Knight et al ., 2012; Graves et al ., 2013). This overlapping function makes it difficult to perturb a single kinase due to cellular feedback mechanisms.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive protein–protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1

DeMille

Bikman

Mathis

et al. 2014

MBoC

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Dissecting phosphorylation networks: lessons learned from yeast

Cited by 15 publications

References 62 publications

An approach for determining and measuring network hierarchy applied to comparing the phosphorylome and the regulome

An approach for determining and measuring network hierarchy applied to comparing the phosphorylome and the regulome

Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in Aspergillus fumigatus

A comprehensive protein–protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1

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