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Regulation of yeast G protein signaling by the kinases that activate the AMPK homolog Snf1.

ABSTRACT: Extracellular signals, such as nutrients and hormones, cue intracellular pathways to produce adaptive responses. Often, cells must coordinate their responses to multiple signals to produce an appropriate outcome. We showed that components of a glucose-sensing pathway acted on components of a heterotrimeric guanine nucleotide-binding protein (G protein)-mediated pheromone signaling pathway in the yeast Saccharomyces cerevisiae. We demonstrated that the G protein ? subunit Gpa1 was phosphorylated in response to conditions of reduced glucose availability and that this phosphorylation event contributed to reduced pheromone-dependent stimulation of mitogen-activated protein kinases, gene transcription, cell morphogenesis, and mating efficiency. We found that Elm1, Sak1, and Tos3, the kinases that phosphorylate Snf1, the yeast homolog of adenosine monophosphate-activated protein kinase (AMPK), in response to limited glucose availability, also phosphorylated Gpa1 and contributed to the diminished mating response. Reg1, the regulatory subunit of the phosphatase PP1 that acts on Snf1, was likewise required to reverse the phosphorylation of Gpa1 and to maintain the mating response. Thus, the same kinases and phosphatase that regulate Snf1 also regulate Gpa1. More broadly, these results indicate that the pheromone signaling and glucose-sensing pathways communicate directly to coordinate cell behavior.

SUBMITTER: Clement ST

PROVIDER: S-EPMC4108480 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Regulation of yeast G protein signaling by the kinases that activate the AMPK homolog Snf1.

Clement Sarah T ST Dixit Gauri G Dohlman Henrik G HG

Science signaling 20130903 291

Extracellular signals, such as nutrients and hormones, cue intracellular pathways to produce adaptive responses. Often, cells must coordinate their responses to multiple signals to produce an appropriate outcome. We showed that components of a glucose-sensing pathway acted on components of a heterotrimeric guanine nucleotide-binding protein (G protein)-mediated pheromone signaling pathway in the yeast Saccharomyces cerevisiae. We demonstrated that the G protein α subunit Gpa1 was phosphorylated ...[more]

PMID: 24003255

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Project description:Sterol regulatory element-binding protein (SREBP), a highly conserved family of membrane-bound transcription factors, is an essential regulator for cellular cholesterol and lipid homeostasis in mammalian cells. Sre1, the homolog of SREBP in the fission yeast Schizosaccharomyces pombe (S. pombe), regulates genes involved in the transcriptional responses to low sterol as well as low oxygen. Previous study reported that casein kinase 1 family member Hhp2 phosphorylated the Sre1 N-terminal transcriptional factor domain (Sre1N) and accelerated Sre1N degradation, and other kinases might exist for regulating the Sre1 function. To gain insight into the mechanisms underlying the Sre1 activity and to identify additional kinases involved in regulation of Sre1 function, we developed a luciferase reporter system to monitor the Sre1 activity through its binding site called SRE2 in living yeast cells. Here we showed that both ergosterol biosynthesis inhibitors and hypoxia-mimic CoCl2 caused a dose-dependent increase in the Sre1 transcription activity, concurrently, these induced transcription activities were almost abolished in ?sre1 cells. Surprisingly, either AMPK? Subunit Ssp2 deletion or Glycogen Synthase Kinases Gsk3/Gsk31 double deletion significantly suppressed ergosterol biosynthesis inhibitors- or CoCl2-induced Sre1 activity. Notably, the ?ssp2?gsk3?gsk31 mutant showed further decreased Sre1 activity when compared with their single or double deletion. Consistently, the ?ssp2?gsk3?gsk31 mutant showed more marked temperature sensitivity than any of their single or double deletion. Moreover, the fluorescence of GFP-Sre1N localized at the nucleus in wild-type cells, but significantly weaker nuclear fluorescence of GFP-Sre1N was observed in ?ssp2, ?gsk3?gsk31, ?ssp2?gsk3, ?ssp2?gsk31 or ?ssp2?gsk3?gsk31 cells. On the other hand, the immunoblot showed a dramatic decrease in GST-Sre1N levels in the ?gsk3?gsk31 or the ?ssp2?gsk3?gsk31 cells but not in the ?ssp2 cells. Altogether, our findings suggest that Gsk3/Gsk31 may regulate Sre1N degradation, while Ssp2 may regulate not only the degradation of Sre1N but also its translocation to the nucleus.

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Regulation of yeast G protein signaling by the kinases that activate the AMPK homolog Snf1.

Publications

Regulation of yeast G protein signaling by the kinases that activate the AMPK homolog Snf1.

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