Efficient transition to growth on fermentable carbon sources in Saccharomyces cerevisiae requires signaling through the Ras pathway

Jiang, Yu; Davis, Corey; Broach, James R.

doi:10.1093/emboj/17.23.6942

Cited by 103 publications

(102 citation statements)

References 51 publications

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“…In contrast to Chiang et al we were unable to find glucose triggered vacuolar degradation of FBPase (Wolf and Ehmann, 1979;Mechler and Wolf, 1981;Teichert et al, 1989;Schork et al, 1994a;Schü le et al, 2000). Because we discovered the participation of some VID-genes in proteasome-linked degradation of FBPase, we repeated catabolite degradation studies of the enzyme in mutants defective in VID22 under our conditions and under conditions used by the laboratories of Chiang (Hoffman and Chiang, 1996) and Broach (Jiang et al, 1998). No stabilization of FBPase was observed under both conditions in the vid22 mutant (our unpublished data; Figure 9B).…”

Section: Discussionmentioning

confidence: 59%

“…The glucose signaling mechanisms for the vacuolar and the proteasomal catabolite degradation pathways of FBPase must be different. In fact, although vacuolar degradation of FBPase was reported to be dependent on the known cAMP-triggered protein kinase A cascade and FBPase phosphorylation (Jiang et al, 1998), the proteasome-dependent degradation pathway of FBPase is not (Hämmerle et al, 1998;Horak et al, 2002). Instead, other signal transduction components such as Grr1p and Reg1p are necessary for proteasomal FBPase degradation (Horak et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Catabolite Degradation of Fructose-1,6-bisphosphatase in the YeastSaccharomyces cerevisiae: A Genome-wide Screen Identifies Eight NovelGIDGenes and Indicates the Existence of Two Degradation Pathways

Regelmann

Schüle

Josupeit

et al. 2003

MBoC

143

186

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Metabolic adaptation of Saccharomyces cerevisiae cells from a nonfermentable carbon source to glucose induces selective, rapid breakdown of the gluconeogenetic key enzyme fructose-1,6-bisphosphatase (FBPase), a process called catabolite degradation. Herein, we identify eight novel GID genes required for proteasome-dependent catabolite degradation of FBPase. Four yeast proteins contain the CTLH domain of unknown function. All of them are Gid proteins. The site of catabolite degradation has been controversial until now. Two FBPase degradation pathways have been described, one dependent on the cytosolic ubiquitin-proteasome machinery, and the other dependent on vacuolar proteolysis. Interestingly, three of the novel Gid proteins involved in ubiquitin-proteasome–dependent degradation have also been reported by others to affect the vacuolar degradation pathway. As shown herein, additional genes suggested to be essential for vacuolar degradation are unnecessary for proteasome-dependent degradation. These data raise the question as to whether two FBPase degradation pathways exist that share components. Detailed characterization of Gid2p demonstrates that it is part of a soluble, cytosolic protein complex of at least 600 kDa. Gid2p is necessary for FBPase ubiquitination. Our studies have not revealed any involvement of vesicular intermediates in proteasome-dependent FBPase degradation. The influence of Ubp14p, a deubiquitinating enzyme, on proteasome-dependent catabolite degradation was further uncovered

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Catabolite Degradation of Fructose-1,6-bisphosphatase in the YeastSaccharomyces cerevisiae: A Genome-wide Screen Identifies Eight NovelGIDGenes and Indicates the Existence of Two Degradation Pathways

Regelmann

Schüle

Josupeit

et al. 2003

MBoC

143

186

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“…Subsequent work also supported a requirement of CDC25 in glucose-induced cAMP signaling (23)(24)(25)(26). The involvement of Ras in glucose-induced cAMP signaling was further supported by the inability of a Ras mutant allele that lacked lipid modification and therefore plasma membrane attachment to mediate glucose-induced cAMP signaling although the allele could support a basal cAMP level high enough for growth (27,28). After Colombo et al (5) showed that only intracellular acidification and not glucose caused an increase in the GTP content on the Ras proteins, attention re-focused on the Gpa2 protein and its G-protein-coupled receptor Gpr1 as a glucose-sensing module required for activation of cAMP synthesis.…”

Section: Involvement Of Ras In Glucose-induced Camp Signaling-mentioning

confidence: 89%

Activation State of the Ras2 Protein and Glucose-induced Signaling in Saccharomyces cerevisiae

Colombo

Ronchetti

Thevelein

et al. 2004

Journal of Biological Chemistry

122

141

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The activity of adenylate cyclase in the yeast Saccharomyces cerevisiae is controlled by two G-protein systems, the Ras proteins and the G␣ protein Gpa2. Glucose activation of cAMP synthesis is thought to be mediated by Gpa2 and its G-protein-coupled receptor Gpr1. Using a sensitive GTP-loading assay for Ras2 we demonstrate that glucose addition also triggers a fast increase in the GTP loading state of Ras2 concomitant with the glucoseinduced increase in cAMP. This increase is severely delayed in a strain lacking Cdc25, the guanine nucleotide exchange factor for Ras proteins. Deletion of the RasGAPs IRA2 (alone or with IRA1) or the presence of RAS2 Val19 allele causes constitutively high Ras GTP loading that no longer increases upon glucose addition. The glucose-induced increase in Ras2 GTP-loading is not dependent on Gpr1 or Gpa2. Deletion of these proteins causes higher GTP loading indicating that the two G-protein systems might directly or indirectly interact. Because deletion of GPR1 or GPA2 reduces the glucoseinduced cAMP increase the observed enhancement of Ras2 GTP loading is not sufficient for full stimulation of cAMP synthesis. Glucose phosphorylation by glucokinase or the hexokinases is required for glucose-induced Ras2 GTP loading. These results indicate that glucose phosphorylation might sustain activation of cAMP synthesis by enhancing Ras2 GTP loading likely through inhibition of the Ira proteins. Strains with reduced feedback inhibition on cAMP synthesis also display elevated basal and induced Ras2 GTP loading consistent with the Ras2 protein acting as a target of the feedback-inhibition mechanism.In Saccharomyces cerevisiae the addition of glucose or other rapidly fermentable sugars to derepressed cells (carbonstarved or growing on a non-fermentable carbon source) triggers a remarkable variety of regulatory phenomena, including many rapid changes at the post-translational and transcriptional level. Several signaling pathways are activated by glucose. One of the best studied pathways is the cAMP/PKA 1 pathway. The main component of this signaling transduction pathway is adenylate cyclase, which catalyzes the synthesis of cAMP. In S. cerevisiae adenylate cyclase activity is controlled by the Ras proteins. These proteins are members of the small GTPase superfamily, which are active in the GTP-bound form and inactive in the GDP-bound form. Recently it has been demonstrated that in S. cerevisiae adenylate cyclase activity is also controlled by a heterotrimeric G␣-protein, Gpa2 (1). A G-protein-coupled receptor, Gpr1, has been identified to be responsible for activation of the Gpa2 protein (2-4). Two triggers are known to activate the cAMP/PKA pathway: the addition of glucose to derepressed cells and intracellular acidification. The Gpr1/Gpa2 G-protein-coupled receptor system is only required for glucose activation of cAMP synthesis (2, 5). The results reported in the literature about the role played by the Ras proteins in activation of cAMP synthesis are in part contradictory. Colombo et al. (5) show...

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“…For the induction with 2-4-dinitrophenol cells were incubated in 25 mM MES buffer (pH 6) for 10 min before addition of 2 mM 2,4-dinitrophenol. Cells were taken by filtration at the time intervals indicated, immediately quenched in n-butanol-saturated 1 M formic acid and frozen in liquid nitrogen (Jiang, Davis, & Broach, 1998). Cell debris was removed by centrifugation and the clear supernatants were freeze dried in a Speed Vac.…”

Section: Camp Determinationmentioning

confidence: 99%

In Saccharomyces cerevisiae an unbalanced level of tyrosine phosphorylation down-regulates the Ras/PKA pathway

Magherini

Busti

Gamberi

et al. 2006

The International Journal of Biochemistry & Cell Biology

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The role of tyrosyl phosphorylation/dephosphorylation in the budding yeast Saccharomyces cerevisiae, whose genome does not encode typical tyrosyne kinases, has long remained elusive. Nevertheless, several protein kinases phosphorylating poly(TyrGlu) substrates have been identified. In this work, we use the expression of the low molecular weight tyrosine phosphatase Stp1 from the distantly related yeast Schizosaccharomyces pombe, as a tool to investigate whether an unbalanced level of protein tyrosine phosphorylation affects S. cerevisiae growth and metabolism. We correlate the previously reported down-regulation of the phosphotyrosine level brought about by overexpression of Stp1 with a large number of phenotypes indicative of down-regulation of the Ras pathway. These phenotypes include reduction in both glucose-and acidification-induced GTP loading of the Ras2 protein and cAMP signaling, impaired growth on a non-fermentable carbon source, alteration of cell cycle parameters, delayed recovery from nitrogen starvation, increased heat-shock resistance, attenuated pseudohyphal and invasive growth. Genetic data suggest that Stp1 acts either at, or above, the level of Ras2, possibly on the Ira proteins. Consistently, Stp1 was found to bind to immunoprecipitated Ira2. Since a catalytically inactive mutant form of Stp1 (Stp1 C11S ) effectively binds to Ira2 without producing any effect on yeast physiology, we conclude that down-regulation of the Ras pathway by Stp1 requires its phosphatase activity. In conclusion, our data suggest a possible cross-talk between tyrosine phosphorylation and the Ras pathway in yeast.

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Efficient transition to growth on fermentable carbon sources in Saccharomyces cerevisiae requires signaling through the Ras pathway

Cited by 103 publications

References 51 publications

Catabolite Degradation of Fructose-1,6-bisphosphatase in the YeastSaccharomyces cerevisiae: A Genome-wide Screen Identifies Eight NovelGIDGenes and Indicates the Existence of Two Degradation Pathways

Catabolite Degradation of Fructose-1,6-bisphosphatase in the YeastSaccharomyces cerevisiae: A Genome-wide Screen Identifies Eight NovelGIDGenes and Indicates the Existence of Two Degradation Pathways

Activation State of the Ras2 Protein and Glucose-induced Signaling in Saccharomyces cerevisiae

In Saccharomyces cerevisiae an unbalanced level of tyrosine phosphorylation down-regulates the Ras/PKA pathway

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