Phosphorylation of the Gα protein Gpa2 promotes protein kinase A signaling in yeast

Huang, Shan; Benben, Alex; Green, Robert C.; Cheranda, Nina; Lee, Grace; Joseph, Benita; Keaveney, Shannon; Wang, Yuqi

doi:10.1074/jbc.ra119.009609

Cited by 6 publications

(7 citation statements)

References 44 publications

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“…cerevisiae contains four mGSK-3 orthologues, MCK1 , MRK1 , YGK3 , and RIM11 , which constitute the GSK-3β family in yeast (yGSK-3β). The percentage identity match of the Rim11 amino acid sequence with those of Mrk1, Mck1, Ygk3, and mouse GSK-3β is 62.3, 41.1, 36.9, and 53.3%, respectively (Supplemental Figure S2), and the proteins have overlapping functions ( Neigeborn and Mitchell, 1991 ; Kassir et al ., 2006 ; Zhou et al ., 2017 ; Huang et al ., 2019 ). This prompted us to investigate whether orthologues other than RIM11 are involved in the GSH stress response.…”

Section: Resultsmentioning

confidence: 99%

Yeast Rim11 kinase responds to glutathione-induced stress by regulating the transcription of phospholipid biosynthetic genes

Yasukawa,

Iwama,

Yamasaki

et al. 2024

MBoC

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Glutathione (GSH), a tripeptide composed of glycine, cysteine, and glutamic acid, is an abundant thiol found in a wide variety of cells, ranging from bacterial to mammalian cells. Adequate levels of GSH are essential for maintaining iron homeostasis. The ratio of oxidized/reduced GSH is strictly regulated in each organelle to maintain the cellular redox potential. Cellular redox imbalances cause defects in physiological activities, which can lead to various diseases. Although there are many reports regarding the cellular response to GSH depletion, studies on stress response to high levels of GSH are limited. Here, we performed genome-scale screening in the yeast Saccharomyces cerevisiae and identified RIM11, BMH1, and WHI2 as multicopy suppressors of the growth defect caused by GSH stress. The deletion strains of each gene were sensitive to GSH. We found that Rim11, a kinase important in the regulation of meiosis, was activated via autophosphorylation upon GSH stress in a glucose-rich medium. Furthermore, RNA-seq revealed that transcription of phospholipid biosynthetic genes was downregulated under GSH stress, and introduction of multiple copies of RIM11 counteracted this effect. These results demonstrate that S. cerevisiae copes with GSH stress via multiple stress-responsive pathways, including a part of the adaptive pathway to glucose limitation.

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Section: Resultsmentioning

confidence: 99%

Yeast Rim11 kinase responds to glutathione-induced stress by regulating the transcription of phospholipid biosynthetic genes

Yasukawa,

Iwama,

Yamasaki

et al. 2024

MBoC

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“…In S. cerevisiae, global phosphoproteomics studies identify Gpa2 as a potential phosphoprotein 67 . Gpa2 undergoes nutrient-regulated phosphorylation, which enhances plasma membrane localization of Gpa2 and promotes protein kinase A activation 47 . Modification of Ime2 in S. cerevisiae is required for the phosphorylation of Gpa2, suggesting a feedback regulation of Ime2 on Gpa2 68 .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies show that Gpa1 interacts with the receptors Ste3 and Gpr5 to activate the Gpa1-cAMP signal pathway, indicating plasma membrane localization of Gpa1 during titan cell production 16,17 . Studies in S. cerevisiae report that changes in G protein phosphorylation levels altered their subcellular localization 47 . Hence, we investigated the subcellular localization of GFP-fused Gpa1 expressed from the ACT1 promoter in H99, crk1Δ, and crk1Δ+CRK1 strain backgrounds.…”

Section: Crk1 Interacts With Gpa1 and Regulates Gpa1 Phosphorylation ...mentioning

confidence: 99%

Ubiquitin proteolysis of a CDK-related kinase regulates titan cell formation and virulence in the fungal pathogen Cryptococcus neoformans

Cao

Wang

et al. 2022

Nat Commun

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Fungal pathogens often undergo morphological switches, including cell size changes, to adapt to the host environment and cause disease. The pathogenic yeast Cryptococcus neoformans forms so-called ‘titan cells’ during infection. Titan cells are large, polyploid, display alterations in cell wall and capsule, and are more resistant to phagocytosis and various types of stress. Titan cell formation is regulated by the cAMP/PKA signal pathway, which is stimulated by the protein Gpa1. Here, we show that Gpa1 is activated through phosphorylation by a CDK-related kinase (Crk1), which is targeted for degradation by an E3 ubiquitin ligase (Fbp1). Strains overexpressing CRK1 or an allele lacking a PEST domain exhibit increased production of titan cells similarly to the fbp1∆ mutant. Conversely, CRK1 deletion results in reduced titan cell production, indicating that Crk1 stimulates titan cell formation. Crk1 phosphorylates Gpa1, which then localizes to the plasma membrane and activates the cAMP/PKA signal pathway to induce cell enlargement. Furthermore, titan cell-overproducing strains trigger increased Th1 and Th17 cytokine production in CD4+ T cells and show attenuated virulence in a mouse model of systemic cryptococcosis. Overall, our study provides insights into the regulation of titan cell formation and fungal virulence.

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“…Phosphorylation of the bovine Gsα (Gs alpha subunit) by epidermal growth factor receptor (EGFR) is exclusive to tyrosine residues and promotes adenylate cyclase [ 69 ]. In Saccharomyces cerevisiae , the alpha subunit Gpa2 is phosphorylated by glycogen synthase kinase (GSK), increasing its localization on the plasma membrane and activating protein kinase A (PKA) at a higher level [ 70 ]. Nevertheless, the characterized phosphorylation sites from these events are not conserved among plant components [ 68 ].…”

Section: Phosphorylation As a Switch Mechanism Of Atgpa1mentioning

confidence: 99%

G-Protein Phosphorylation: Aspects of Binding Specificity and Function in the Plant Kingdom

Oliveira

Jones

Fontes

et al. 2022

IJMS

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Plant survival depends on adaptive mechanisms that constantly rely on signal recognition and transduction. The predominant class of signal discriminators is receptor kinases, with a vast member composition in plants. The transduction of signals occurs in part by a simple repertoire of heterotrimeric G proteins, with a core composed of α-, β-, and γ-subunits, together with a 7-transmembrane Regulator G Signaling (RGS) protein. With a small repertoire of G proteins in plants, phosphorylation by receptor kinases is critical in regulating the active state of the G-protein complex. This review describes the in vivo detected phosphosites in plant G proteins and conservation scores, and their in vitro corresponding kinases. Furthermore, recently described outcomes, including novel arrestin-like internalization of RGS and a non-canonical phosphorylation switching mechanism that drives G-protein plasticity, are discussed.

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Phosphorylation of the Gα protein Gpa2 promotes protein kinase A signaling in yeast

Cited by 6 publications

References 44 publications

Yeast Rim11 kinase responds to glutathione-induced stress by regulating the transcription of phospholipid biosynthetic genes

Yeast Rim11 kinase responds to glutathione-induced stress by regulating the transcription of phospholipid biosynthetic genes

Ubiquitin proteolysis of a CDK-related kinase regulates titan cell formation and virulence in the fungal pathogen Cryptococcus neoformans

G-Protein Phosphorylation: Aspects of Binding Specificity and Function in the Plant Kingdom

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