Roles of the Snf1-Activating Kinases during Nitrogen Limitation and Pseudohyphal Differentiation in
            <i>Saccharomyces cerevisiae</i>

Orlova, Marianna; Ozcetin, Hamit; Barrett, LaKisha; Kuchin, Sergei

doi:10.1128/ec.00216-09

Cited by 25 publications

(23 citation statements)

References 65 publications

(44 reference statements)

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“…The involvement of PKA could therefore account for a portion of the glucose signal affecting Snf1. In addition to glucose signaling, Snf1 participates in responses to other stress conditions, such as nitrogen limitation and exposure to rapamycin (41,52,53). PKA is involved in nitrogen and TOR signaling (see reference 82 for a review) and could mediate a relevant signal(s) impinging on Snf1.…”

Section: Discussionmentioning

confidence: 99%

“…Except for 4011774 and 4013278, all strains were in the ⌺1278b genetic background and were descendants of strains MY1384 (MATa; prototroph), MY1401 (MAT␣ ura3⌬ leu2⌬ his3⌬), and MY1402 (MATa ura3⌬ leu2⌬ trp1⌬) of the isogenic Sigma2000 series (Microbia, Cambridge, MA). ⌺1278b derivatives carrying reg1⌬::URA3, snf1::LEU2, snf1⌬::KanMX6, and sak1⌬::KanMX4 have been described (40,52,53); additional derivatives were obtained by genetic crossing and tetrad analysis. To generate ⌺1278b derivatives with ira1⌬::KanMX6, ira2⌬:: KanMX6, ira2⌬::His3MX6, bcy1⌬::KanMX6, and gpr1⌬::KanMX6, the marker sequences were amplified by PCR with primers flanking the corresponding open reading frames.…”

Section: Methodsmentioning

confidence: 99%

“…To construct plasmid pMK9-6, the wild-type SAK1 gene, including 0.72 kb of its upstream regulatory sequence, was amplified by PCR from genomic DNA, cloned into pCRII-TOPO using the TOPO TA cloning kit (Invitrogen), sequenced, and then excised and ligated into the ApaI site of the low-copy-number vector pRS315 (63). pMK11-3 was constructed similarly, except that the (53). pKB2 was derived from pM31-8 by introducing a mutation that changes the Ser1074 codon of SAK1 to an Ala codon, using the QuikChange XL site-directed mutagenesis kit (Stratagene) and a pair of complementary mutagenic primers that also create a silent diagnostic BssHII site overlapping the Ala1074 codon; the construct was confirmed by sequencing.…”

Section: Methodsmentioning

confidence: 99%

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Protein Kinase A Contributes to the Negative Control of Snf1 Protein Kinase in Saccharomyces cerevisiae

et al. 2012

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Snf1 protein kinase regulates responses to glucose limitation and other stresses. Snf1 activation requires phosphorylation of its T-loop threonine by partially redundant upstream kinases (Sak1, Tos3, and Elm1). Under favorable conditions, Snf1 is turned off by Reg1-Glc7 protein phosphatase. The reg1 mutation causes increased Snf1 activation and slow growth. To identify new components of the Snf1 pathway, we searched for mutations that, like snf1, suppress reg1 for the slow-growth phenotype. In addition to mutations in genes encoding known pathway components (SNF1, SNF4, and SAK1), we recovered "fast" mutations, designated fst1 and fst2. Unusual morphology of the mutants in the ⌺1278b strains employed here helped us identify fst1 and fst2 as mutations in the RasGAP genes IRA1 and IRA2. Cells lacking Ira1, Ira2, or Bcy1, the negative regulatory subunit of cyclic AMP (cAMP)-dependent protein kinase A (PKA), exhibited reduced Snf1 pathway activation. Conversely, Snf1 activation was elevated in cells lacking the Gpr1 sugar receptor, which contributes to PKA signaling. We show that the Snf1-activating kinase Sak1 is phosphorylated in vivo on a conserved serine (Ser1074) within an ideal PKA motif. However, this phosphorylation alone appears to play only a modest role in regulation, and Sak1 is not the only relevant target of the PKA pathway. Collectively, our results suggest that PKA, which integrates multiple regulatory inputs, could contribute to Snf1 regulation under various conditions via a complex mechanism. Our results also support the view that, like its mammalian counterpart, AMP-activated protein kinase (AMPK), yeast Snf1 participates in metabolic checkpoint control that coordinates growth with nutrient availability.T he Snf1/AMP-activated protein kinase (AMPK) family is highly conserved in eukaryotes, and its members control responses to metabolic stress (reviewed in references 22, 23, and 26). Mammalian AMPK is activated by increased intracellular AMPto-ATP ratios under energy-depleting conditions, such as hypoglycemia and hypoxia. AMPK is also regulated by hormones that control whole-body metabolism, including leptin, adiponectin, and ghrelin. Activated AMPK functions to restore energy equilibrium by stimulating ATP-generating pathways and by inhibiting energy-consuming processes. Important functions of AMPK include stimulation of glucose uptake and fatty acid oxidation, as well as downregulation of protein synthesis and cell growth. Accordingly, defects in AMPK signaling have been linked to diseases from diabetes and obesity to cancer, making AMPK a promising target for activation with drugs (reviewed in references 15 and 21).In the yeast Saccharomyces cerevisiae, Snf1 protein kinase is the ortholog of mammalian AMPK. The most established role of Snf1 is to regulate responses to glucose limitation (for a review, see reference 26). As glucose levels decrease, Snf1 is activated and promotes the use of less preferred (alternative) carbon sources. Activation of Snf1 results from phosphorylation of its conserve...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Protein Kinase A Contributes to the Negative Control of Snf1 Protein Kinase in Saccharomyces cerevisiae

et al. 2012

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“…These proteins might also sensitize MAPK activity to other nutrient levels. In particular, filamentous growth can be regulated by limiting nitrogen (Gimeno et al 1992), which is sensed by the Snf1-activating kinase Sak1 (Orlova et al 2010). A link between the AMPK and MAPK pathways has been actively sought in higher eukaryotes, and several connections have been reported.…”

Section: Mig1 and Mig2 Proteins Connect Glucose Signaling To Mapk Regmentioning

confidence: 99%

The Filamentous Growth MAPK Pathway Responds to Glucose Starvation Through the Mig1/2 Transcriptional Repressors in Saccharomyces cerevisiae

Karunanithi

Cullen

2012

Genetics

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In the budding yeast S. cerevisiae, nutrient limitation induces a MAPK pathway that regulates filamentous growth and biofilm/mat formation. How nutrient levels feed into the regulation of the filamentous growth pathway is not entirely clear. We characterized a newly identified MAPK regulatory protein of the filamentous growth pathway, Opy2. A two-hybrid screen with the cytosolic domain of Opy2 uncovered new interacting partners including a transcriptional repressor that functions in the AMPK pathway, Mig1, and its close functional homolog, Mig2. Mig1 and Mig2 coregulated the filamentous growth pathway in response to glucose limitation, as did the AMP kinase Snf1. In addition to associating with Opy2, Mig1 and Mig2 interacted with other regulators of the filamentous growth pathway including the cytosolic domain of the signaling mucin Msb2, the MAP kinase kinase Ste7, and the MAP kinase Kss1. As for Opy2, Mig1 overproduction dampened the pheromone response pathway, which implicates Mig1 and Opy2 as potential regulators of pathway specificity. Taken together, our findings provide the first regulatory link in yeast between components of the AMPK pathway and a MAPK pathway that controls cellular differentiation.

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“…An interesting question to address will also be how the two pathways co-operate to trigger the ability to accumulate glucose and whether they measure distinct signals, such as lack of extracellular glucose or reduced energy status. Interestingly, both the Ras/PKA and Snf1 pathways are also involved in control of pseudohyphal growth under conditions of nitrogen starvation [38,39]. Since both pathways are predominantly affected by sugars and energy status, the two pathways may act as an input of low carbon supply/energy status into the checkpoint that controls entry into pseudohyphal growth.…”

Section: Discussionmentioning

confidence: 97%

Differential regulation of glucose transport activity in yeast by specific cAMP signatures

Bermejo

Haerizadeh

Sadoine

et al. 2013

Biochemical Journal

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Successful colonization and survival in variable environments require a competitive advantage during the initial growth phase after experiencing nutrient changes. Starved yeast cells anticipate exposure to glucose by activating the Hxt5p (hexose transporter 5) glucose transporter, which provides an advantage during early phases after glucose resupply. cAMP and glucose FRET (fluorescence resonance energy transfer) sensors were used to identify three signalling pathways that co-operate in the anticipatory Hxt5p activity in glucose-starved cells: as expected the Snf1 (sucrose nonfermenting 1) AMP kinase pathway, but, surprisingly, the sugar-dependent G-protein-coupled Gpr1 (G-protein-coupled receptor 1)/cAMP/PKA (protein kinase A) pathway and the Pho85 (phosphate metabolism 85)/Plc (phospholipase C) 6/7 pathway. Gpr1/cAMP/PKA are key elements of a G-protein-coupled sugar response pathway that produces a transient cAMP peak to induce growth-related genes. A novel function of the Gpr1/cAMP/PKA pathway was identified in glucose-starved cells: during starvation the Gpr1/cAMP/PKA pathway is required to maintain Hxt5p activity in the absence of glucose-induced cAMP spiking. During starvation, cAMP levels remain low triggering expression of HXT5, whereas cAMP spiking leads to a shift to the high capacity Hxt isoforms.

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Roles of the Snf1-Activating Kinases during Nitrogen Limitation and Pseudohyphal Differentiation in Saccharomyces cerevisiae

Cited by 25 publications

References 65 publications

Protein Kinase A Contributes to the Negative Control of Snf1 Protein Kinase in Saccharomyces cerevisiae

Protein Kinase A Contributes to the Negative Control of Snf1 Protein Kinase in Saccharomyces cerevisiae

The Filamentous Growth MAPK Pathway Responds to Glucose Starvation Through the Mig1/2 Transcriptional Repressors in Saccharomyces cerevisiae

Differential regulation of glucose transport activity in yeast by specific cAMP signatures

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