Journal articles: 'Gpa2'

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Shen, Gui, Yan-Li Wang, Amy Whittington, Lie Li, and Ping Wang. "The RGS Protein Crg2 Regulates Pheromone and Cyclic AMP Signaling in Cryptococcus neoformans." Eukaryotic Cell 7, no. 9 (July 25, 2008): 1540–48. http://dx.doi.org/10.1128/ec.00154-08.

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ABSTRACT Crg1 and Crg2 are regulators of G-protein signaling homologs found in the human fungal pathogen Cryptococcus neoformans. Crg1 negatively regulates pheromone responses and mating through direct inhibition of Gα subunits Gpa2 and Gpa3. It has also been proposed that Crg2 has a role in mating, as genetic crosses involving Δcrg2 mutants resulted in formation of hyperfilaments. We found that mutation of Gpa2 and Gpa3 partially suppressed the hyperfilamentation, mutation of Gpa3 alleviated Δcrg2-specfic cell swelling, and mutation of the mitogen-activated protein kinase Cpk1 blocked both processes. These findings indicate that Gpa2 and Gpa3 function downstream of Crg2 and that Gpa3 is also epistatic to Crg2 in a Cpk1-dependent morphogenesis process linked to mating. Significantly, we found that Δcrg2 mutants formed enlarged capsules that mimic cells expressing a constitutively active GPA1(Q284L) allele and that the levels of intracellular cyclic AMP (cAMP) were also elevated, suggesting that Crg2 also negatively regulates the Gpa1-cAMP signaling pathway. We further showed that Crg2 interacted with Gpa3 and Gpa1, but not Gpa2, in a pulldown assay and that Crg2 maintained a higher in vitro GTPase-activating protein activity toward Gpa3 and Gpa1 than to Gpa2. Finally, we found that dysregulation of cAMP due to the Crg2 mutation attenuated virulence in a murine model of cryptococcosis. Taken together, our study reveals Crg2 as an RGS (regulator of G-protein signaling) protein of multiregulatory function, including one that controls mating distinctly from Crg1 and one that serves as a novel inhibitor of Gpa1-cAMP signaling.

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Hsueh, Yen-Ping, Chaoyang Xue, and Joseph Heitman. "G protein signaling governing cell fate decisions involves opposing Gα subunits inCryptococcus neoformans." Molecular Biology of the Cell 18, no. 9 (September 2007): 3237–49. http://dx.doi.org/10.1091/mbc.e07-02-0133.

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Communication between cells and their environments is often mediated by G protein-coupled receptors and cognate G proteins. In fungi, one such signaling cascade is the mating pathway triggered by pheromone/pheromone receptor recognition. Unlike Saccharomyces cerevisiae, which expresses two Gα subunits, most filamentous ascomycetes and basidiomycetes have three Gα subunits. Previous studies have defined the Gα subunit acting upstream of the cAMP-protein kinase A pathway, but it has been unclear which Gα subunit is coupled to the pheromone receptor and response pathway. Here we report that in the pathogenic basidiomycetous yeast Cryptococcus neoformans, two Gα subunits (Gpa2, Gpa3) sense pheromone and govern mating. gpa2 gpa3 double mutants, but neither gpa2 nor gpa3 single mutants, are sterile in bilateral crosses. By contrast, deletion of GPA3 (but not GPA2) constitutively activates pheromone response and filamentation. Expression of GPA2 and GPA3 is differentially regulated: GPA3 expression is induced by nutrient-limitation, whereas GPA2 is induced during mating. Based on the phenotype of dominant active alleles, Gpa2 and Gpa3 signal in opposition: Gpa2 promotes mating, whereas Gpa3 inhibits. The incorporation of an additional Gα into the regulatory circuit enabled increased signaling complexity and facilitated cell fate decisions involving choice between yeast growth and filamentous asexual/sexual development.

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Gong, Jinjun, Jacob D. Grodsky, Zhengguang Zhang, and Ping Wang. "A Ric8/Synembryn Homolog Promotes Gpa1 and Gpa2 Activation To Respectively Regulate Cyclic AMP and Pheromone Signaling in Cryptococcus neoformans." Eukaryotic Cell 13, no. 10 (August 1, 2014): 1290–99. http://dx.doi.org/10.1128/ec.00109-14.

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ABSTRACTThe G protein α subunits Gpa1, Gpa2, and Gpa3 mediate signal transduction and are important in the growth and virulence ofCryptococcus neoformans. To understand how Gpa1 functions without a conventional Gβ subunit, we characterized a resistance to inhibitors of cholinesterase 8 (Ric8) homolog fromC. neoformans, which shares amino acid sequence homology with other Ric8 proteins that exhibit guanine nucleotide exchange factor (GEF) activity toward Gα. We found that theric8mutant was reduced in capsule size and melanin formation, which could be suppressed by cyclic AMP (cAMP) supplementation or by introducing the activatedGPA1Q284Lallele. Consistent with the fact that Ric8 participates in cAMP signaling to regulate virulence, theric8mutant was attenuated in virulence toward mice. Interestingly, disruption ofRIC8also resulted in opposing effects on pheromone signaling, as theric8mutant showed reduced mating but an enhanced ability to induce the pheromone response in the mating partner. To identify Ric8 functional mechanisms, we examined the interactions between Ric8 and the three Gα proteins. Ric8 interacted with Gpa1 and Gpa2, but not Gpa3. The presence of Gpa1Q284Lnegatively affected its interaction with Ric8, whereas the activated Gpa2Q203Lallele abolished the interaction. Collectively, these findings suggest that Ric8 functions as a GEF to facilitate the activation of Gpa1-cAMP signaling and to promote Gpa2, affecting mating efficiency. Our study highlights the distinct and conserved characteristics associated with G protein signaling and contributes to our overall understanding of how G protein α subunits function with or without a canonical Gβ partner inC. neoformans.

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Harashima, Toshiaki, and Joseph Heitman. "Gα Subunit Gpa2 Recruits Kelch Repeat Subunits That Inhibit Receptor-G Protein Coupling during cAMP-induced Dimorphic Transitions in Saccharomyces cerevisiae." Molecular Biology of the Cell 16, no. 10 (October 2005): 4557–71. http://dx.doi.org/10.1091/mbc.e05-05-0403.

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All eukaryotic cells sense extracellular stimuli and activate intracellular signaling cascades via G protein-coupled receptors (GPCR) and associated heterotrimeric G proteins. The Saccharomyces cerevisiae GPCR Gpr1 and associated Gα subunit Gpa2 sense extracellular carbon sources (including glucose) to govern filamentous growth. In contrast to conventional Gα subunits, Gpa2 forms an atypical G protein complex with the kelch repeat Gβ mimic proteins Gpb1 and Gpb2. Gpb1/2 negatively regulate cAMP signaling by inhibiting Gpa2 and an as yet unidentified target. Here we show that Gpa2 requires lipid modifications of its N-terminus for membrane localization but association with the Gpr1 receptor or Gpb1/2 subunits is dispensable for membrane targeting. Instead, Gpa2 promotes membrane localization of its associated Gβ mimic subunit Gpb2. We also show that the Gpa2 N-terminus binds both to Gpb2 and to the C-terminal tail of the Gpr1 receptor and that Gpb1/2 binding interferes with Gpr1 receptor coupling to Gpa2. Our studies invoke novel mechanisms involving GPCR-G protein modules that may be conserved in multicellular eukaryotes.

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Li, Lie, Gui Shen, Zheng-Guang Zhang, Yan-Li Wang, Jill K. Thompson, and Ping Wang. "Canonical Heterotrimeric G Proteins Regulating Mating and Virulence ofCryptococcus neoformans." Molecular Biology of the Cell 18, no. 11 (November 2007): 4201–9. http://dx.doi.org/10.1091/mbc.e07-02-0136.

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Perturbation of pheromone signaling modulates not only mating but also virulence in Cryptococcus neoformans, an opportunistic human pathogen known to encode three Gα, one Gβ, and two Gγ subunit proteins. We have found that Gαs Gpa2 and Gpa3 exhibit shared and distinct roles in regulating pheromone responses and mating. Gpa2 interacted with the pheromone receptor homolog Ste3α, Gβ subunit Gpb1, and RGS protein Crg1. Crg1 also exhibited in vitro GAP activity toward Gpa2. These findings suggest that Gpa2 regulates mating through a conserved signaling mechanism. Moreover, we found that Gγs Gpg1 and Gpg2 both regulate pheromone responses and mating. gpg1 mutants were attenuated in mating, and gpg2 mutants were sterile. Finally, although gpa2, gpa3, gpg1, gpg2, and gpg1 gpg2 mutants were fully virulent, gpa2 gpa3 mutants were attenuated for virulence in a murine model. Our study reveals a conserved but distinct signaling mechanism by two Gα, one Gβ, and two Gγ proteins for pheromone responses, mating, and virulence in Cryptococcus neoformans, and it also reiterates that the link between mating and virulence is not due to mating per se but rather to certain mating-pathway components that encode additional functions promoting virulence.

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Meza-Carmen, Victor, Jesús García-Soto, Laura Ongay-Larios, Roberto Coria, Mario Pedraza-Reyes, José Arnau, Georgina Reyna-Lopez, and Guadalupe Martínez-Cadena. "Molecular characterization of a G protein α-subunit-encoding gene fromMucor circinelloides." Canadian Journal of Microbiology 52, no. 7 (July 1, 2006): 627–35. http://dx.doi.org/10.1139/w06-010.

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Genes encoding the Gα subunit were cloned from Mucor circinelloides, a zygomycete dimorphic fungus. There are at least four genes that encode for Gα subunits, gpa1, gpa2, gpa3, and gpa4. The genes gpa1 and gpa3 were isolated and characterized, and their predicted products showed 36%–67% identity with Gα subunits from diverse fungi. Northern blot analysis of gpa3 showed that it is present in spores and constitutively expressed during mycelium development and during yeast–mycelium and mycelium–yeast transitions. However, during yeast cell growth, decreased levels of mRNA were observed. Sequence analysis of gpa3 cDNA revealed that Gpa3 encodes a polypeptide of 356 amino acids with a calculated molecular mass of 40.8 kDa. The deduced sequence of Gpa3 protein contains all the consensus regions of Gα subunits of the Gαi/o/tsubfamily except the cysteine near the C terminus for potential ADP-ribosylation by pertussis toxin. This cDNA was expressed in Escherichia coli and purified by affinity chromatography. Based on its electrophoretic mobility in SDS–PAGE, the molecular mass of the His6-tagged Gpa3 was 45 kDa. The recombinant protein was recognized by a polyclonal antibody against a fragment of a human Gαi/o/t. Furthermore, the recombinant Gpa3 was ADP-ribosylated by activated cholera toxin and [32P]NAD but not by pertussis toxin. These results indicate that in M. circinelloides the Gα subunit Gpa3 is expressed constitutively during differentiation.Key words: Gα-subunit-encoding genes, Mucor circinelloides, Gpa3 recombinant protein.

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Landry, Sheila, Maria T. Pettit, Ethel Apolinario, and Charles S. Hoffman. "The Fission Yeast git5 Gene Encodes a Gβ Subunit Required for Glucose-Triggered Adenylate Cyclase Activation." Genetics 154, no. 4 (April 1, 2000): 1463–71. http://dx.doi.org/10.1093/genetics/154.4.1463.

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Abstract Fission yeast adenylate cyclase is activated by the gpa2 Gα subunit of a heterotrimeric guanine-nucleotide binding protein (G protein). We show that the git5 gene, also required for this activation, encodes a Gβ subunit. In contrast to another study, we show that git5 is not a negative regulator of the gpa1 Gα involved in the pheromone response pathway. While 43% identical to mammalian Gβ's, the git5 protein lacks the amino-terminal coiled-coil found in other Gβ subunits, yet the gene possesses some of the coding capacity for this structure 5′ to its ORF. Although both gpa2 (Gα) and git5 (Gβ) are required for adenylate cyclase activation, only gpa2 is needed to maintain basal cAMP levels. Strains bearing a git5 disruption are derepressed for fbp1 transcription and sexual development even while growing in a glucose-rich environment, although fbp1 derepression is half that observed in gpa2 deletion strains. Multicopy gpa2 partially suppresses the loss of git5, while the converse is not true. These data suggest that Gβ is required for activation of adenylate cyclase either by promoting the activation of Gα or by independently activating adenylate cyclase subsequent to Gα stimulation as seen in type II mammalian adenylate cyclase activation.

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Ivey, F. Douglas, Francis X. Taglia, Fan Yang, Matthew M. Lander, David A. Kelly, and Charles S. Hoffman. "Activated Alleles of the Schizosaccharomyces pombegpa2+ Gα Gene Identify Residues Involved in GDP-GTP Exchange." Eukaryotic Cell 9, no. 4 (February 5, 2010): 626–33. http://dx.doi.org/10.1128/ec.00010-10.

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ABSTRACT The Schizosaccharomyces pombe glucose/cyclic AMP (cAMP) signaling pathway includes the Gpa2-Git5-Git11 heterotrimeric G protein, whose Gpa2 Gα subunit directly binds to and activates adenylate cyclase in response to signaling from the Git3 G protein-coupled receptor. To study intrinsic and extrinsic regulation of Gpa2, we developed a plasmid-based screen to identify mutationally activated gpa2 alleles that bypass the loss of the Git5-Git11 Gβγ dimer to repress transcription of the glucose-regulated fbp1 + gene. Fifteen independently isolated mutations alter 11 different Gpa2 residues, with all but one conferring a receptor-independent activated phenotype upon integration into the gpa2 + chromosomal locus. Biochemical characterization of three activated Gpa2 proteins demonstrated an increased GDP-GTP exchange rate that would explain the mechanism of activation. Interestingly, the amino acid altered in the Gpa2(V90A) exchange rate mutant protein is in a region of Gpa2 with no obvious role in Gα function, thus extending our understanding of Gα protein structure-function relationships.

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Miwa, Takuya, Yukinobu Takagi, Makiko Shinozaki, Cheol-Won Yun, Wiley A. Schell, John R. Perfect, Hidehiko Kumagai, and Hisanori Tamaki. "Gpr1, a Putative G-Protein-Coupled Receptor, Regulates Morphogenesis and Hypha Formation in the Pathogenic Fungus Candida albicans." Eukaryotic Cell 3, no. 4 (August 2004): 919–31. http://dx.doi.org/10.1128/ec.3.4.919-931.2004.

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ABSTRACT In response to various extracellular signals, the morphology of the human fungal pathogen Candida albicans switches from yeast to hypha form. Here, we report that GPR1 encoding a putative G-protein-coupled receptor and GPA2 encoding a Gα subunit are required for hypha formation and morphogenesis in C. albicans. Mutants lacking Gpr1 (gpr1/gpr1) or Gpa2 (gpa2/gpa2) are defective in hypha formation and morphogenesis on solid hypha-inducing media. These phenotypic defects in solid cultures are suppressed by exogenously added dibutyryl-cyclic AMP (dibutyryl-cAMP). Biochemical studies also reveal that GPR1 and GPA2 are required for a glucose-dependent increase in cellular cAMP. An epistasis analysis indicates that Gpr1 functions upstream of Gpa2 in the same signaling pathway, and a two-hybrid assay reveals that the carboxyl-terminal tail of Gpr1 interacts with Gpa2. Moreover, expression levels of HWP1 and ECE1, which are cAMP-dependent hypha-specific genes, are reduced in both mutant strains. These findings support a model that Gpr1, as well as Gpa2, regulates hypha formation and morphogenesis in a cAMP-dependent manner. In contrast, GPR1 and GPA2 are not required for hypha formation in liquid fetal bovine serum (FBS) medium. Furthermore, the gpr1 and the gpa2 mutant strains are fully virulent in a mouse infection. These findings suggest that Gpr1 and Gpa2 are involved in the glucose-sensing machinery that regulates morphogenesis and hypha formation in solid media via a cAMP-dependent mechanism, but they are not required for hypha formation in liquid medium or during invasive candidiasis.

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Sudo, Satoko, Yoshimitsu Kuwabara, Jae-Il Park, Sheau Yu Hsu, and Aaron J. W. Hsueh. "Heterodimeric Fly Glycoprotein Hormone-α2 (GPA2) and Glycoprotein Hormone-β5 (GPB5) Activate Fly Leucine-Rich Repeat-Containing G Protein-Coupled Receptor-1 (DLGR1) and Stimulation of Human Thyrotropin Receptors by Chimeric Fly GPA2 and Human GPB5." Endocrinology 146, no. 8 (August 1, 2005): 3596–604. http://dx.doi.org/10.1210/en.2005-0317.

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Abstract Glycoprotein hormones play important roles in thyroid and gonadal function in vertebrates. The glycoprotein hormone α-subunit forms heterodimers with different β-subunits to activate TSH or gonadotropin (LH and FSH) receptors. Recent genomic analyses allowed the identification of another α-subunit, GPA2, and another β-subunit, GPB5, in human, capable of forming heterodimers to activate TSH receptors. Based on comparative genomic searches, we isolated the fly orthologs for human GPA2 and GPB5, each consisting of 10 cysteine residues likely involved in cystine-knot formation. RT-PCR analyses in Drosophila melanogaster demonstrated the expression of GPA2 and GPB5 at different developmental stages. Immunoblot analyses further showed that fly GPA2 and GPB5 subunit proteins are of approximately 16 kDa, and coexpression of these subunits yielded heterodimers. Purified recombinant fly GPA2/GPB5 heterodimers were found to be glycoproteins with N-linked glycosylated α-subunits and nonglycosylated β-subunits, capable of stimulating cAMP production mediated by fly orphan receptor DLGR1 but not DLGR2. Although the fly GPA2/GPB5 heterodimers did not activate human TSH or gonadotropin receptors, chimeric fly GPA2/human GPB5 heterodimers stimulated human TSH receptors. These findings indicated that fly GPA2/GPB5 is a ligand for DLGR1, thus showing the ancient origin of this glycoprotein hormone-seven transmembrane receptor-G protein signaling system. The fly GPA2 also could form heterodimers with human GPB5 to activate human TSH receptors, indicating the evolutionary conservation of these genes and suggesting that the GPA2 subunit may serve as a scaffold for the β-subunit to activate downstream G protein-mediated signaling.

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Sánchez-Martínez, Cristina, and José Pérez-Martín. "Gpa2, a G-Protein α Subunit Required for Hyphal Development in Candida albicans." Eukaryotic Cell 1, no. 6 (December 2002): 865–74. http://dx.doi.org/10.1128/ec.1.6.865-874.2002.

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ABSTRACT Candida albicans is able to respond to environmental changes by inducing a distinct morphological program, which is related to the ability to infect mammalian hosts. Although some of the signal transduction pathways involved in this response are known, it is not clear how the environmental signals are sensed and transmitted to these transduction cascades. In this work, we have studied the function of GPA2, a new gene from C. albicans, which encodes a G-protein α-subunit homologue. We demonstrate that Gpa2 plays an important role in the yeast-hypha dimorphic transition in the response of C. albicans to some environmental inducers. Deletion of both alleles of the GPA2 gene causes in vitro defects in morphological transitions in Spider medium and SLAD medium and in embedded conditions but not in medium containing serum. These defects cannot be reversed by exogenous addition of cyclic AMP. However, overexpression of HST7, which encodes a component of the filament-inducing mitogen-activated protein kinase (MAPK) cascade, bypasses the Gpa2 requirement. We have obtained different gain-of-function and loss-of-function mutant alleles of the GPA2 gene, which we have introduced in several C. albicans genetic backgrounds. Our results indicate that, in response to environmental cues, Gpa2 is required for the regulation of a MAPK signaling pathway.

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Mudge, Dayna K., Fan Yang, Brian M. Currie, James M. Kim, Kelly Yeda, Varoon K. Bashyakarla, F. Douglas Ivey, and Charles S. Hoffman. "Sck1 Negatively Regulates Gpa2-Mediated Glucose Signaling in Schizosaccharomyces pombe." Eukaryotic Cell 13, no. 2 (December 2, 2013): 202–8. http://dx.doi.org/10.1128/ec.00277-13.

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ABSTRACTSchizosaccharomyces pombedetects extracellular glucose via a G protein-mediated cyclic AMP (cAMP)-signaling pathway activating protein kinase A (PKA) and regulating transcription of genes involved in metabolism and sexual development. In this pathway, Gpa2 Gα binds to and activates adenylyl cyclase in response to glucose detection by the Git3 G protein-coupled receptor. Using a two-hybrid screen to identify extrinsic regulators of Gpa2, we isolated a clone that expresses codons 471 to 696 of the Sck1 kinase, which appears to display a higher affinity for Gpa2K270E-activated Gα relative to Gpa2+Gα. Deletion ofsck1+or mutational inactivation of the Sck1 kinase produces phenotypes reflecting increased PKA activity in strains expressing Gpa2+or Gpa2K270E, suggesting that Sck1 negatively regulates PKA activation through Gpa2. In contrast to the Gpa2K270EGDP-GTP exchange rate mutant, GTPase-defective Gpa2R176Hweakly binds Sck1 in the two-hybrid screen and a deletion ofsck1+in a Gpa2R176Hstrain confers phenotypes consistent with a slight reduction in PKA activity. Finally, deletingsck1+in agpa2Δ strain results in phenotypes consistent with a second role for Sck1 acting in parallel with PKA. In addition to this parallel role with PKA, our data suggest that Sck1 negatively regulates Gpa2, possibly targeting the nucleotide-free form of the protein that may expose the one and only AKT/PKB consensus site in Gpa2 for Sck1 to bind. This dual role for Sck1 may allowS. pombeto produce distinct biological responses to glucose and nitrogen starvation signals that both activate the Wis1-Spc1/StyI stress-activated protein kinase (SAPK) pathway.

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Dos Santos, Sandra, Claire Bardet, Stephanie Bertrand, Hector Escriva, Damien Habert, and Bruno Querat. "Distinct Expression Patterns of Glycoprotein Hormone-α2 and -β5 in a Basal Chordate Suggest Independent Developmental Functions." Endocrinology 150, no. 8 (May 3, 2009): 3815–22. http://dx.doi.org/10.1210/en.2008-1743.

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The vertebrate glycoprotein hormones (GpHs), gonadotropins and thyrotropin, are heterodimers composed of a common α- and specific β-subunit. The recombinant heterodimer of two additional, structurally related proteins identified in vertebrate and protostome genomes, the glycoproteins-α2 (GPA2) and-β5 (GPB5), was shown to activate the thyrotropin receptor and was therefore named thyrostimulin. However, differences in tissue distribution and expression levels of these proteins suggested that they might act as nonassociated factors, prompting further investigation on these proteins. In this study we show that GPA2 and GPB5 appeared with the emergence of bilateria and were maintained in most groups. These genes are tightly associated at the genomic level, an association, however, lost in tetrapods. Our structural and genomic environment comparison reinforces the hypothesis of their phylogenetic relationships with GpH-α and -β. In contrast, the glycosylation status of GPA2 and GPB5 is highly variable further questioning heterodimer secretory efficiency and activity. As a first step toward understanding their function, we investigated the spatiotemporal expression of GPA2 and GPB5 genes at different developmental stages in a basal chordate, the amphioxus. Expression of GPB5 was essentially ubiquitous with an anteroposterior gradient in embryos. GPA2 embryonic and larvae expression was restricted to specific areas and, interestingly, partially overlapped that of a GpH receptor-related gene. In conclusion, we speculate that GPA2 and GPB5 have nondispensable and coordinated functions related to a novelty appeared with bilateria. These proteins would be active during embryonic development in a manner that does not require their heterodimerization.

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Nocero, M., T. Isshiki, M. Yamamoto, and C. S. Hoffman. "Glucose repression of fbp1 transcription of Schizosaccharomyces pombe is partially regulated by adenylate cyclase activation by a G protein alpha subunit encoded by gpa2 (git8)." Genetics 138, no. 1 (September 1, 1994): 39–45. http://dx.doi.org/10.1093/genetics/138.1.39.

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Abstract In the fission yeast Schizosaccharomyces pombe, genetic studies have identified genes that are required for glucose repression of fbp1 transcription. The git2 gene, also known as cyr1, encodes adenylate cyclase. Adenylate cyclase converts ATP into the second messenger cAMP as part of many eukaryotic signal transduction pathways. The git1, git3, git5, git7, git8 and git10 genes act upstream of adenylate cyclase, presumably encoding an adenylate cyclase activation pathway. In mammalian cells, adenylate cyclase enzymatic activity is regulated by heterotrimeric guanine nucleotide-binding proteins (G proteins). In the budding yeast Saccharomyces cerevisiae, adenylate cyclase enzymatic activity is regulated by monomeric, guanine nucleotide-binding Ras proteins. We show here that git8 is identical to the gpa2 gene that encodes a protein homologous to the alpha subunit of a G protein. Mutations in two additional genes, git3 and git5 are suppressed by gpa2+ in high copy number. Furthermore, a mutation in either git3 or git5 has an additive effect in strains deleted for gpa2 (git8), as it significantly increases expression of an fbp1-lacZ reporter gene. Therefore, git3 and git5 appear to act either in concert with or independently from gpa2 (git8) to regulate adenylate cyclase activity.

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van der Voort, Jeroen Rouppe, Konstantin Kanyuka, Edwin van der Vossen, Abdelhafid Bendahmane, Paul Mooijman, René Klein-Lankhorst, Willem Stiekema, David Baulcombe, and Jaap Bakker. "Tight Physical Linkage of the Nematode Resistance Gene Gpa2 and the Virus Resistance Gene Rx on a Single Segment Introgressed from the Wild Species Solanum tuberosum subsp. andigena CPC 1673 into Cultivated Potato." Molecular Plant-Microbe Interactions® 12, no. 3 (March 1999): 197–206. http://dx.doi.org/10.1094/mpmi.1999.12.3.197.

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Comparative mapping studies within several plant genera have shown that genes for resistance to taxonomically diverse pathogens are often co-localized on the maps of these genotypes. Here we describe the genetic analysis of such a gene cluster on chromosome 12 of potato. This cluster harbors the resistance loci Gpa2 and Rx, which confer resistance to the potato cyst nematode Globodera pallida and potato virus X (PVX), respectively. By screening two mapping populations with 10 CAPS (cleaved amplified polymorphic sequence) markers derived from AFLP (amplified fragment length polymorphism) markers and the ends of overlapping bacterial artificial chromosome (BAC) clones, it is demonstrated that Gpa2 and Rx are tightly linked. From a recombination fraction of 1/3386, found after screening two different mapping populations, a genetic distance of 0.02 cM between Gpa2 and Rx was calculated. The physical length of this genetic interval does not exceed 300 kb of DNA as determined by the total size of overlapping BAC clones in the Rx/Gpa2 contig. Evidence is provided that both genes have been introgressed from a single wild species clone, Solanum tuberosum subsp. andigena CPC 1673. This suggests that these genes underlying the disease resistance specificities to potato virus X and potato cyst nematodes have a common evolutionary origin.

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Landry, Sheila, and Charles S. Hoffman. "The git5 Gβ and git11 Gγ Form an Atypical Gβγ Dimer Acting in the Fission Yeast Glucose/cAMP Pathway." Genetics 157, no. 3 (March 1, 2001): 1159–68. http://dx.doi.org/10.1093/genetics/157.3.1159.

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AbstractFission yeast adenylate cyclase, like mammalian adenylate cyclases, is regulated by a heterotrimeric G protein. The gpa2 Gα and git5 Gβ are both required for glucose-triggered cAMP signaling. The git5 Gβ is a unique member of the Gβ family in that it lacks an amino-terminal coiled-coil domain shown to be essential for mammalian Gβ folding and interaction with Gγ subunits. Using a git5 bait in a two-hybrid screen, we identified the git11 Gγ gene. Co-immunoprecipitation studies confirm the composition of this Gβγ dimer. Cells deleted for git11 are defective in glucose repression of both fbp1 transcription and sexual development, resembling cells lacking either the gpa2 Gα or the git5 Gβ. Overexpression of the gpa2 Gα partially suppresses loss of either the git5 Gβ or the git11 Gγ, while mutational activation of the Gα fully suppresses loss of either Gβ or Gγ. Deletion of gpa2 (Gα), git5 (Gβ), or git11 (Gγ) confer quantitatively distinct effects on fbp1 repression, indicating that the gpa2 Gα subunit remains partially active in the absence of the Gβγ dimer and that the git5 Gβ subunit remains partially active in the absence of the git11 Gγ subunit. The addition of the CAAX box from the git11 Gγ to the carboxy-terminus of the git5 Gβ partially suppresses the loss of the Gγ. Thus the Gγ in this system is presumably required for localization of the Gβγ dimer but not for folding of the Gβ subunit. In mammalian cells, the essential roles of the Gβ amino-terminal coiled-coil domains and Gγ partners in Gβ folding may therefore reflect a mechanism used by cells that express multiple forms of both Gβ and Gγ subunits to regulate the composition and activity of its G proteins.

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Hsu, Sheau Yu, Koji Nakabayashi, and Alka Bhalla. "Evolution of Glycoprotein Hormone Subunit Genes in Bilateral Metazoa: Identification of Two Novel Human Glycoprotein Hormone Subunit Family Genes, GPA2 and GPB5." Molecular Endocrinology 16, no. 7 (July 1, 2002): 1538–51. http://dx.doi.org/10.1210/mend.16.7.0871.

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Abstract The canonical members of the human glycoprotein hormone subunit family of cystine knot-forming polypeptides include the common α-subunit, and four β-subunit genes, FSHβ, LHβ, TSHβ, and hCGβ. Using pairwise sequence analysis of the complete human genome, we have identified two novel glycoprotein hormone subunit-related genes. Based on unique sequence similarity to the α- and β-subunits of glycoprotein hormones, they were named glycoprotein-α2 (GPA2) and glycoprotein-β5 (GPB5), respectively. PCR analysis using a panel of human cDNAs from 14 different tissues demonstrated that GPB5 is similar to other β-subunits showing restricted tissue expression, mainly in pituitary and brain. In contrast, the GPA2 transcript is found in diverse tissues. Furthermore, immunoreactive GPA2 and GPB5 were detected in the anterior pituitary of mouse and frog, whereas the expression of GPA2 and GPB5 in transfected cells resulted in the secretion of recombinant polypeptides in conditioned medium. After GenBank searches in lower organisms, glycoprotein hormone β-subunit-related genes were identified from the genome of nematode Caenorhabditis elegans, hookworm Ancylostoma caninum, and Drosophila melanogaster. The evolutionary conservation of these invertebrate homologs can be seen in several key sequence characteristics, and the data suggest that the glycoprotein hormone β-subunit gene ancestor evolved before the emergence of bilateral metazoa, thus providing a better understanding of the evolution of this group of classic polypeptide hormones and their receptors. Studies of the complete inventory of genes homologous to glycoprotein hormone subunits in the human genome and lower organisms will allow future functional characterization and identification of their respective receptors.

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Donzeau, Mariel, and Wolfhard Bandlow. "The Yeast Trimeric Guanine Nucleotide-Binding Protein α Subunit, Gpa2p, Controls the Meiosis-Specific Kinase Ime2p Activity in Response to Nutrients." Molecular and Cellular Biology 19, no. 9 (September 1, 1999): 6110–19. http://dx.doi.org/10.1128/mcb.19.9.6110.

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ABSTRACT Saccharomyces cerevisiae Gpa2p, the α subunit of a heterotrimeric guanine nucleotide-binding protein (G protein), is involved in the regulation of vegetative growth and pseudohyphal development. Here we report that Gpa2p also controls sporulation by interacting with the regulatory domain of Ime2p (Sme1p), a protein kinase essential for entrance of meiosis and sporulation. Protein-protein interactions between Gpa2p and Ime2p depend on the GTP-bound state of Gpa2p and correlate with down-regulation of Ime2p kinase activity in vitro. Overexpression of Ime2p inhibits pseudohyphal development and enables diploid cells to sporulate even in the presence of glucose or nitrogen. In contrast, overexpression of Gpa2p in cells simultaneously overproducing Ime2p results in a drastic reduction of sporulation efficiency, demonstrating an inhibitory effect of Gpa2p on Ime2p function. Furthermore, deletion of GPA2 accelerates sporulation on low-nitrogen medium. These observations are consistent with the following model. In glucose-containing medium, diploid cells do not sporulate because Ime2p is inactive or expressed at low levels. Upon starvation, expression of Gpa2p and Ime2p is induced but sporulation is prevented as long as nitrogen is present in the medium. The negative control of Ime2p kinase activity is exerted at least in part through the activated form of Gpa2p and is released as soon as nutrients are exhausted. This model attributes a switch function to Gpa2p in the meiosis-pseudohyphal growth decision.

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Chasse, Scott A., Paul Flanary, Stephen C. Parnell, Nan Hao, Jiyoung Y. Cha, David P. Siderovski, and Henrik G. Dohlman. "Genome-Scale Analysis Reveals Sst2 as the Principal Regulator of Mating Pheromone Signaling in the Yeast Saccharomyces cerevisiae." Eukaryotic Cell 5, no. 2 (February 2006): 330–46. http://dx.doi.org/10.1128/ec.5.2.330-346.2006.

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ABSTRACT A common property of G protein-coupled receptors is that they become less responsive with prolonged stimulation. Regulators of G protein signaling (RGS proteins) are well known to accelerate G protein GTPase activity and do so by stabilizing the transition state conformation of the G protein α subunit. In the yeast Saccharomyces cerevisiae there are four RGS-homologous proteins (Sst2, Rgs2, Rax1, and Mdm1) and two Gα proteins (Gpa1 and Gpa2). We show that Sst2 is the only RGS protein that binds selectively to the transition state conformation of Gpa1. The other RGS proteins also bind Gpa1 and modulate pheromone signaling, but to a lesser extent and in a manner clearly distinct from Sst2. To identify other candidate pathway regulators, we compared pheromone responses in 4,349 gene deletion mutants representing nearly all nonessential genes in yeast. A number of mutants produced an increase (sst2, bar1, asc1, and ygl024w) or decrease (cla4) in pheromone sensitivity or resulted in pheromone-independent signaling (sst2, pbs2, gas1, and ygl024w). These findings suggest that Sst2 is the principal regulator of Gpa1-mediated signaling in vivo but that other proteins also contribute in distinct ways to pathway regulation.

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Bassett, J. H. Duncan, Anne van der Spek, John G. Logan, Apostolos Gogakos, Jayashree Bagchi-Chakraborty, Elaine Murphy, Clementine van Zeijl, et al. "Thyrostimulin Regulates Osteoblastic Bone Formation During Early Skeletal Development." Endocrinology 156, no. 9 (September 1, 2015): 3098–113. http://dx.doi.org/10.1210/en.2014-1943.

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The ancestral glycoprotein hormone thyrostimulin is a heterodimer of unique glycoprotein hormone subunit alpha (GPA)2 and glycoprotein hormone subunit beta (GPB)5 subunits with high affinity for the TSH receptor. Transgenic overexpression of GPB5 in mice results in cranial abnormalities, but the role of thyrostimulin in bone remains unknown. We hypothesized that thyrostimulin exerts paracrine actions in bone and determined: 1) GPA2 and GPB5 expression in osteoblasts and osteoclasts, 2) the skeletal consequences of thyrostimulin deficiency in GPB5 knockout (KO) mice, and 3) osteoblast and osteoclast responses to thyrostimulin treatment. Gpa2 and Gpb5 expression was identified in the newborn skeleton but declined rapidly thereafter. GPA2 and GPB5 mRNAs were also expressed in primary osteoblasts and osteoclasts at varying concentrations. Juvenile thyrostimulin-deficient mice had increased bone volume and mineralization as a result of increased osteoblastic bone formation. However, thyrostimulin failed to induce a canonical cAMP response or activate the noncanonical Akt, ERK, or mitogen-activated protein kinase (P38) signaling pathways in primary calvarial or bone marrow stromal cell-derived osteoblasts. Furthermore, thyrostimulin did not directly inhibit osteoblast proliferation, differentiation or mineralization in vitro. These studies identify thyrostimulin as a negative but indirect regulator of osteoblastic bone formation during skeletal development.

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Cheranda, Nina Kiran, Shan Huang, and Yuqi Wang. "Investigating the Effects of Gpa2 Phosphorylation on Yeast Sporulation." FASEB Journal 34, S1 (April 2020): 1. http://dx.doi.org/10.1096/fasebj.2020.34.s1.02710.

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Li, Shuang, Yuanyuan Li, Blake R. Rushing, Sarah E. Harris, Susan L. McRitchie, Janice C. Jones, Daniel Dominguez, Susan J. Sumner, and Henrik G. Dohlman. "Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1." PLOS Genetics 17, no. 7 (July 2, 2021): e1009640. http://dx.doi.org/10.1371/journal.pgen.1009640.

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Heterotrimeric G proteins were originally discovered through efforts to understand the effects of hormones, such as glucagon and epinephrine, on glucose metabolism. On the other hand, many cellular metabolites, including glucose, serve as ligands for G protein-coupled receptors. Here we investigate the consequences of glucose-mediated receptor signaling, and in particular the role of a Gα subunit Gpa2 and a non-canonical Gβ subunit, known as Asc1 in yeast and RACK1 in animals. Asc1/RACK1 is of particular interest because it has multiple, seemingly unrelated, functions in the cell. The existence of such “moonlighting” operations has complicated the determination of phenotype from genotype. Through a comparative analysis of individual gene deletion mutants, and by integrating transcriptomics and metabolomics measurements, we have determined the relative contributions of the Gα and Gβ protein subunits to glucose-initiated processes in yeast. We determined that Gpa2 is primarily involved in regulating carbohydrate metabolism while Asc1 is primarily involved in amino acid metabolism. Both proteins are involved in regulating purine metabolism. Of the two subunits, Gpa2 regulates a greater number of gene transcripts and was particularly important in determining the amplitude of response to glucose addition. We conclude that the two G protein subunits regulate distinct but complementary processes downstream of the glucose-sensing receptor, as well as processes that lead ultimately to changes in cell growth and metabolism.

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Pan, Xuewen, and Joseph Heitman. "Cyclic AMP-Dependent Protein Kinase Regulates Pseudohyphal Differentiation in Saccharomyces cerevisiae." Molecular and Cellular Biology 19, no. 7 (July 1, 1999): 4874–87. http://dx.doi.org/10.1128/mcb.19.7.4874.

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ABSTRACT In response to nitrogen starvation, diploid cells of the yeastSaccharomyces cerevisiae differentiate to a filamentous growth form known as pseudohyphal differentiation. Filamentous growth is regulated by elements of the pheromone mitogen-activated protein (MAP) kinase cascade and a second signaling cascade involving the receptor Gpr1, the Gα protein Gpa2, Ras2, and cyclic AMP (cAMP). We show here that the Gpr1-Gpa2-cAMP pathway signals via the cAMP-dependent protein kinase, protein kinase A (PKA), to regulate pseudohyphal differentiation. Activation of PKA by mutation of the regulatory subunit Bcy1 enhances filamentous growth. Mutation and overexpression of the PKA catalytic subunits reveal that the Tpk2 catalytic subunit activates filamentous growth, whereas the Tpk1 and Tpk3 catalytic subunits inhibit filamentous growth. The PKA pathway regulates unipolar budding and agar invasion, whereas the MAP kinase cascade regulates cell elongation and invasion. Epistasis analysis supports a model in which PKA functions downstream of the Gpr1 receptor and the Gpa2 and Ras2 G proteins. Activation of filamentous growth by PKA does not require the transcription factors Ste12 and Tec1 of the MAP kinase cascade, Phd1, or the PKA targets Msn2 and Msn4. PKA signals pseudohyphal growth, in part, by regulating Flo8-dependent expression of the cell surface flocculin Flo11. In summary, the cAMP-dependent protein kinase plays an intimate positive and negative role in regulating filamentous growth, and these findings may provide insight into the roles of PKA in mating, morphogenesis, and virulence in other yeasts and pathogenic fungi.

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Welton, Robert M., and Charles S. Hoffman. "Glucose Monitoring in Fission Yeast via the gpa2 Gα, the git5 Gβ and the git3 Putative Glucose Receptor." Genetics 156, no. 2 (October 1, 2000): 513–21. http://dx.doi.org/10.1093/genetics/156.2.513.

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Abstract The fission yeast Schizosaccharomyces pombe responds to environmental glucose by activating adenylate cyclase. The resulting cAMP signal activates protein kinase A (PKA). PKA inhibits glucose starvation-induced processes, such as conjugation and meiosis, and the transcription of the fbp1 gene that encodes the gluconeogenic enzyme fructose-1,6-bisphosphatase. We previously identified a collection of git genes required for glucose repression of fbp1 transcription, including pka1/git6, encoding the PKA catalytic subunit, git2/cyr1, encoding adenylate cyclase, and six “upstream” genes required for adenylate cyclase activation. The git8 gene, identical to gpa2, encodes the alpha subunit of a heterotrimeric guanine-nucleotide binding protein (Gα) while git5 encodes a Gβ subunit. Multicopy suppression studies with gpa2+ previously indicated that S. pombe adenylate cyclase activation may resemble that of the mammalian type II enzyme with sequential activation by Gα followed by βγ. We show here that an activated allele of gpa2 (gpa2R176H, carrying a mutation in the coding region for the GTPase domain) fully suppresses mutations in git3 and git5, leading to a refinement in our model. We describe the cloning of git3 and show that it encodes a putative seven-transmembrane G protein-coupled receptor. A git3 deletion confers the same phenotypes as deletions of other components of the PKA pathway, including a germination delay, constitutive fbp1 transcription, and starvation-independent conjugation. Since the git3 deletion is fully suppressed by the gpa2R176H allele with respect to fbp1 transcription, git3 appears to encode a G protein-coupled glucose receptor responsible for adenylate cyclase activation in S. pombe.

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Lorenz, Michael C., Xuewen Pan, Toshiaki Harashima, Maria E. Cardenas, Yong Xue, Jeanne P. Hirsch, and Joseph Heitman. "The G Protein-Coupled Receptor Gpr1 Is a Nutrient Sensor That Regulates Pseudohyphal Differentiation in Saccharomyces cerevisiae." Genetics 154, no. 2 (February 1, 2000): 609–22. http://dx.doi.org/10.1093/genetics/154.2.609.

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Abstract Pseudohyphal differentiation in the budding yeast Saccharomyces cerevisiae is induced in diploid cells in response to nitrogen starvation and abundant fermentable carbon source. Filamentous growth requires at least two signaling pathways: the pheromone responsive MAP kinase cascade and the Gpa2p-cAMP-PKA signaling pathway. Recent studies have established a physical and functional link between the Gα protein Gpa2 and the G protein-coupled receptor homolog Gpr1. We report here that the Gpr1 receptor is required for filamentous and haploid invasive growth and regulates expression of the cell surface flocculin Flo11. Epistasis analysis supports a model in which the Gpr1 receptor regulates pseudohyphal growth via the Gpa2p-cAMP-PKA pathway and independently of both the MAP kinase cascade and the PKA related kinase Sch9. Genetic and physiological studies indicate that the Gpr1 receptor is activated by glucose and other structurally related sugars. Because expression of the GPR1 gene is known to be induced by nitrogen starvation, the Gpr1 receptor may serve as a dual sensor of abundant carbon source (sugar ligand) and nitrogen starvation. In summary, our studies reveal a novel G protein-coupled receptor senses nutrients and regulates the dimorphic transition to filamentous growth via a Gα protein-cAMP-PKA signal transduction cascade.

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Hoffman, C. S. "Glucose sensing via the protein kinase A pathway in Schizosaccharomyces pombe." Biochemical Society Transactions 33, no. 1 (February 1, 2005): 257–60. http://dx.doi.org/10.1042/bst0330257.

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The fission yeast Schizosaccharomyces pombe primarily detects glucose via a cAMP-signalling pathway. Components of this pathway include the Git3 G-protein-coupled receptor and a heterotrimeric G-protein, from which the Gpa2 Gα subunit activates adenylate cyclase (Git2/Cyr1). Three additional proteins, Git1, Git7 and Git10 are required to generate a cAMP response even in a strain expressing an activated form of Gpa2, which is capable of bypassing the loss of the GPCR and Gβγ dimer. Therefore, Git1, Git7 and Git10 either act in a G-protein-independent manner or are required to stabilize or assemble a functional signalling complex. Although prior data suggested that the Cgs2 cAMP phosphodiesterase (PDE) does not regulate the cAMP response, we now have evidence that along with adenylate cyclase regulation, PDE activation is important for limiting the response to glucose. Finally, regulation of protein kinase A activation appears to involve both traditional post-translational regulation of the function of the components of the cAMP pathway and glucose-dependent transcriptional regulation of some of these cAMP pathway genes.

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Park, Young-Un, Hyangsuk Hur, Minhan Ka, and Jinmi Kim. "Identification of Translational Regulation Target Genes during Filamentous Growth in Saccharomyces cerevisiae: Regulatory Role of Caf20 and Dhh1." Eukaryotic Cell 5, no. 12 (October 13, 2006): 2120–27. http://dx.doi.org/10.1128/ec.00121-06.

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ABSTRACT The dimorphic transition of yeast to the hyphal form is regulated by the mitogen-activated protein kinase and cyclic AMP-dependent protein kinase A pathways in Saccharomyces cerevisiae. Signaling pathway-responsive transcription factors such as Ste12, Tec1, and Flo8 are known to mediate filamentation-specific transcription. We were interested in investigating the translational regulation of specific mRNAs during the yeast-to-hyphal-form transition. Using polyribosome fractionation and RT-PCR analysis, we identified STE12, GPA2, and CLN1 as translation regulation target genes during filamentous growth. The transcript levels for these genes did not change, but their mRNAs were preferentially associated with polyribosomes during the hyphal transition. The intracellular levels of Ste12, Gpa2, and Cln1 proteins increased under hyphal-growth conditions. The increase in Ste12 protein level was partially blocked by mutations in the CAF20 and DHH1 genes, which encode an eIF4E inhibitor and a decapping activator, respectively. In addition, the caf20 and dhh1 mutations resulted in defects in filamentous growth. The filamentation defects caused by caf20 and dhh1 mutations were suppressed by STE12 overexpression. These results suggest that Caf20 and Dhh1 control yeast filamentation by regulating STE12 translation.

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Lorenz, M. C. "Yeast pseudohyphal growth is regulated by GPA2, a G protein alpha homolog." EMBO Journal 16, no. 23 (December 1, 1997): 7008–18. http://dx.doi.org/10.1093/emboj/16.23.7008.

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Huang, Shan, Alex Benben, Robert Green, Nina Cheranda, Grace Lee, Benita Joseph, Shannon Keaveney, and Yuqi Wang. "Phosphorylation of the Gα protein Gpa2 promotes protein kinase A signaling in yeast." Journal of Biological Chemistry 294, no. 49 (November 5, 2019): 18836–45. http://dx.doi.org/10.1074/jbc.ra119.009609.

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Hausken, Krist N., Belen Tizon, Michal Shpilman, Shannon Barton, Wayne Decatur, David Plachetzki, Scott Kavanaugh, Sabah Ul-Hasan, Berta Levavi-Sivan, and Stacia A. Sower. "Cloning and characterization of a second lamprey pituitary glycoprotein hormone, thyrostimulin (GpA2/GpB5)." General and Comparative Endocrinology 264 (August 2018): 16–27. http://dx.doi.org/10.1016/j.ygcen.2018.04.010.

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Wang, Ying, Michael Pierce, Lisa Schneper, C. Gökçe Güldal, Xiuying Zhang, Saeed Tavazoie, and James R. Broach. "Ras and Gpa2 Mediate One Branch of a Redundant Glucose Signaling Pathway in Yeast." PLoS Biology 2, no. 5 (May 11, 2004): e128. http://dx.doi.org/10.1371/journal.pbio.0020128.

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Al-Dailami, Areej N., Jimena Leyria, Ian Orchard, and Angela B. Lange. "Exploring the role of glycoprotein hormone GPA2/GPB5 in the medically important insect, Rhodnius prolixus." Peptides 149 (March 2022): 170710. http://dx.doi.org/10.1016/j.peptides.2021.170710.

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Sacco, Melanie Ann, Kamila Koropacka, Eric Grenier, Marianne J. Jaubert, Alexandra Blanchard, Aska Goverse, Geert Smant, and Peter Moffett. "The Cyst Nematode SPRYSEC Protein RBP-1 Elicits Gpa2- and RanGAP2-Dependent Plant Cell Death." PLoS Pathogens 5, no. 8 (August 28, 2009): e1000564. http://dx.doi.org/10.1371/journal.ppat.1000564.

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Bakulina, A. V., L. S. Savintseva, O. N. Bashlakova, and N. F. Sintsova. "Molecular screening of potato varieties bred by Falenki Breeding station for resistance to phytopathogens." Agricultural Science Euro-North-East 22, no. 3 (June 25, 2021): 340–50. http://dx.doi.org/10.30766/2072-9081.2021.22.3.340-350.

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The genotypes of potatoes bred by Falenki Breeding station were studied for the presence of resistance genes markers to the following pathogens: Globodera rostochiensis, Globodera pallidа, Synchytrium endobioticum, potato virus X (PVХ) and potato virus Y (PVY). The method of multiplex PCR analysis was used. The varieties Shurminsky 2, Alisa, Viza, Chayka, Ognivo, Darik, Gloriya, Golubka, Virazh and a promising variety sample 56-09 were studied. In most (8 out of 10) genotypes, marker linked to the Sen1 gene of resistance to S. endobioticum was identified. DNA marker of the G. rostochiensis resistance gene (H1) and the G. pallida resistance gene marker (Gpa2) were found in six genotypes. The marker of the PVX resistance gene (Rx1) was detected in the varieties Shurminsky 2, Alisa, Chayka, Golubka, and Virazh. It has been established that none of the studied potato genotypes carries markers RYSC3, Ry186, YES3-3A linked to the PVY resistance genes. Although in the field, resistance was detected in the samples Chayka, Darik, Virazh, Alisa. Molecular markers linked to the largest number of resistance genes studied (H1, Gpa2, Sen1, and Rx1) were identified in the varieties Shurminsky 2, Golubka, and Virazh. Among the DNA markers used in the work, the data of potato genotype assessment using markers of virus resistance genes (PVX, RYSC3, Ry186, YES3-3A) were less consistent with field observations. The use of molecular markers makes it possible to determine the presence of resistance genes and assess the prospects of a sample in a short period of time, but, at the same time, requires careful choice of a DNA marker that is highly correlated with the manifestation of the trait.

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Tando, Yukiko, and Kaoru Kubokawa. "A Homolog of the Vertebrate Thyrostimulin Glycoprotein Hormone α Subunit (GPA2) is Expressed in Amphioxus Neurons." Zoological Science 26, no. 6 (June 2009): 409–14. http://dx.doi.org/10.2108/zsj.26.409.

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Bennett, Richard J., and Alexander D. Johnson. "The role of nutrient regulation and the Gpa2 protein in the mating pheromone response ofC. albicans." Molecular Microbiology 62, no. 1 (August 29, 2006): 100–119. http://dx.doi.org/10.1111/j.1365-2958.2006.05367.x.

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Rocco, David A., and Jean-Paul V. Paluzzi. "Functional role of the heterodimeric glycoprotein hormone, GPA2/GPB5, and its receptor, LGR1: An invertebrate perspective." General and Comparative Endocrinology 234 (August 2016): 20–27. http://dx.doi.org/10.1016/j.ygcen.2015.12.011.

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Ivey, F. D., and C. S. Hoffman. "Direct activation of fission yeast adenylate cyclase by the Gpa2 G of the glucose signaling pathway." Proceedings of the National Academy of Sciences 102, no. 17 (April 14, 2005): 6108–13. http://dx.doi.org/10.1073/pnas.0502270102.

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Stakheev, Alexander A., Denis V. Erokhin, Ekaterina A. Meleshchuk, Oleg D. Mikityuk, and Natalia V. Statsyuk. "Effect of Compactin on the Mycotoxin Production and Expression of Related Biosynthetic and Regulatory Genes in Toxigenic Fusarium culmorum." Microorganisms 10, no. 7 (July 4, 2022): 1347. http://dx.doi.org/10.3390/microorganisms10071347.

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Zearalenone (ZEN) and deoxynivalenol (DON) are mycotoxins produced by various species of Fusarium fungi. They contaminate agricultural products and negatively influence human and animal health, thus representing a serious problem of the agricultural industry. Earlier we showed that compactin, a secondary metabolite of Penicillium citrinum, is able to completely suppress the aflatoxin B1 biosynthesis by Aspergillus flavus. Using the F. culmorum strain FC-19 able to produce DON and ZEN, we demonstrated that compactin also significantly suppressed both DON (99.3%) and ZEN (100%) biosynthesis. The possible mechanisms of this suppression were elucidated by qPCR-based analysis of expression levels of 48 biosynthetic and regulatory genes. Expression of eight of 13 TRI genes, including TRI4, TRI5, and TRI101, was completely suppressed. A significant down-regulation was revealed for the TRI10, TRI9, and TRI14 genes. TRI15 was the only up-regulated gene from the TRI cluster. In the case of the ZEN cluster, almost complete suppression was observed for PKS4, PKS13, and ZEB1 genes, and the balance between two ZEB2 isoforms was altered. Among regulatory genes, an increased expression of GPA1 and GPA2 genes encoding α- and β-subunits of a G-protein was shown, whereas eight genes were down-regulated. The obtained results suggest that the main pathway for a compactin-related inhibition of the DON and ZEN biosynthesis affects the transcription of genes involved in the G-protein-cAMP-PKA signaling pathway. The revealed gene expression data may provide a better understanding of genetic mechanisms underlying mycotoxin production and its regulation.

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Sellami, Azza, Hans-Jürgen Agricola, and Jan A. Veenstra. "Neuroendocrine cells in Drosophila melanogaster producing GPA2/GPB5, a hormone with homology to LH, FSH and TSH." General and Comparative Endocrinology 170, no. 3 (February 2011): 582–88. http://dx.doi.org/10.1016/j.ygcen.2010.11.015.

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Harashima, Toshiaki, and Joseph Heitman. "The Gα Protein Gpa2 Controls Yeast Differentiation by Interacting with Kelch Repeat Proteins that Mimic Gβ Subunits." Molecular Cell 10, no. 1 (July 2002): 163–73. http://dx.doi.org/10.1016/s1097-2765(02)00569-5.

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Papasawas, Savvas, Steve Arkinstall, John Reid, and Mark Payton. "Yeast α-mating factor receptor and G-protein-linked adenylyl cyclase inhibition requires RAS2 and GPA2 activities." Biochemical and Biophysical Research Communications 184, no. 3 (May 1992): 1378–85. http://dx.doi.org/10.1016/s0006-291x(05)80035-x.

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Karasawa, Ken, Kazunari Tanigawa, Ayako Harada, and Atsushi Yamashita. "Transcriptional Regulation of Acyl-CoA:Glycerol-sn-3-Phosphate Acyltransferases." International Journal of Molecular Sciences 20, no. 4 (February 22, 2019): 964. http://dx.doi.org/10.3390/ijms20040964.

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Acyl-CoA:glycerol-sn-3-phosphate acyltransferase (GPAT) is an enzyme responsible for the rate-limiting step in the synthesis of glycerophospholipids and triacylglycerol (TAG). The enzymes of mammalian species are classified into four isoforms; GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, whereas GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane. The activity of each enzyme expressed is associated with physiological and pathological functions. The transcriptional regulation is well known, particularly in GPAT1. GPAT1 mRNA expression is mainly regulated by the binding of the transcriptional factor SREBP-1c to the specific element (the sterol regulatory element) flanking the GPAT1 promoter. The TAG level is controlled by the insulin-induced transcriptional expression of GPAT1, which occupies most of the GPAT activity in the liver. The transcriptional regulation of the other three GPAT isoforms remains undetermined in detail. It is predicted that retinoic acid serves as a transcription factor in the GPAT2 promoter. PPARγ (peroxisome proliferator-activated receptor γ) increases the mRNA expression of GPAT3, which is associated with TAG synthesis in adipose tissues. Although GPAT has been considered to be a key enzyme in the production of TAG, unexpected functions have recently been reported, particularly in GPAT2. It is likely that GPAT2 is associated with tumorigenesis and normal spermatogenesis. In this review, the physiological and pathophysiological roles of the four GPAT isoforms are described, alongside the transcriptional regulation of these enzymes.

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Rocco, David A., Doo Hyun Kim, and Jean-Paul V. Paluzzi. "Immunohistochemical mapping and transcript expression of the GPA2/GPB5 receptor in tissues of the adult mosquito, Aedes aegypti." Cell and Tissue Research 369, no. 2 (April 11, 2017): 313–30. http://dx.doi.org/10.1007/s00441-017-2610-3.

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van der Voort, J. Rouppe, P. Wolters, R. Folkertsma, R. Hutten, P. van Zandvoort, H. Vinke, K. Kanyuka, et al. "Mapping of the cyst nematode resistance locus Gpa2 in potato using a strategy based on comigrating AFLP markers." Theoretical and Applied Genetics 95, no. 5-6 (October 1997): 874–80. http://dx.doi.org/10.1007/s001220050638.

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Paluzzi, Jean-Paul, Mark Vanderveken, and Michael J. O’Donnell. "The Heterodimeric Glycoprotein Hormone, GPA2/GPB5, Regulates Ion Transport across the Hindgut of the Adult Mosquito, Aedes aegypti." PLoS ONE 9, no. 1 (January 20, 2014): e86386. http://dx.doi.org/10.1371/journal.pone.0086386.

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Yang, Chien-Chung, Li-Der Hsiao, Ya-Fang Shih, Chih-Kai Hsu, Chia-Yu Hu, and Chuen-Mao Yang. "Thrombin Induces COX-2 and PGE2 Expression via PAR1/PKCalpha/MAPK-Dependent NF-kappaB Activation in Human Tracheal Smooth Muscle Cells." Mediators of Inflammation 2022 (April 19, 2022): 1–18. http://dx.doi.org/10.1155/2022/4600029.

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The inflammation of the airway and lung could be triggered by upregulation cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) induced by various proinflammatory factors. COX-2 induction by thrombin has been shown to play a vital role in various inflammatory diseases. However, in human tracheal smooth muscle cells (HTSMCs), how thrombin enhanced the levels of COX-2/PGE2 is not completely characterized. Thus, in this study, the levels of COX-2 expression and PGE2 synthesis induced by thrombin were determined by Western blot, promoter-reporter assay, real-time PCR, and ELISA kit. The various signaling components involved in the thrombin-mediated responses were differentiated by transfection with siRNAs and selective pharmacological inhibitors. The role of NF-κB was assessed by a chromatin immunoprecipitation (ChIP) assay, immunofluorescent staining, as well as Western blot. Our results verified that thrombin markedly triggered PGE2 secretion via COX-2 upregulation which were diminished by the inhibitor of thrombin (PPACK), PAR1 (SCH79797), Gi/o protein (GPA2), Gq protein (GPA2A), PKCα (Gö6976), p38 MAPK (SB202190), JNK1/2 (SP600125), MEK1/2 (U0126), or NF-κB (helenalin) and transfection with siRNA of PAR1, Gqα, Giα, PKCα, JNK2, p38, p42, or p65. Moreover, thrombin induced PAR1-dependent PKCα phosphorylation in HTSMCs. We also observed that thrombin induced p38 MAPK, JNK1/2, and p42/p44 MAPK activation through a PAR1/PKCα pathway. Thrombin promoted phosphorylation of NF-κB p65, leading to nuclear translocation and binding to the COX-2 promoter element to enhance promoter activity, which was reduced by Gö6976, SP600125, SB202190, or U0126. These findings supported that COX-2/PGE2 expression triggered by thrombin was engaged in PAR1/Gq or Gi/o/PKCα/MAPK-dependent NF-κB activation in HTSMCs.

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Isshiki, T., N. Mochizuki, T. Maeda, and M. Yamamoto. "Characterization of a fission yeast gene, gpa2, that encodes a G alpha subunit involved in the monitoring of nutrition." Genes & Development 6, no. 12b (December 1, 1992): 2455–62. http://dx.doi.org/10.1101/gad.6.12b.2455.

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Vanoni, M., R. L. Rossi, L. Querin, V. Zinzalla, and L. Alberghina. "Glucose modulation of cell size in yeast." Biochemical Society Transactions 33, no. 1 (February 1, 2005): 294–96. http://dx.doi.org/10.1042/bst0330294.

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Saccharomyces cerevisiae cells grown in glucose have larger average size than cells grown in ethanol. Besides, yeast must reach a carbon source-modulated critical cell size in order to enter S phase at Start. This control is of outmost physiological relevance, since it allows us to coordinate cell growth with cell cycle progression and it is responsible for cell size homeostasis. The cell sizer mechanism requires the overcoming of two sequential thresholds, involving Cln3 and Far1, and Clb5,6 and Sic1, respectively. When both thresholds are non-functional, carbon source modulation of cell size at Start is completely abolished. Since inactivation of extracellular glucose sensing through deletion of either the GPR1 or the GPA2 gene causes a marked, but partial, reduction in the ability to modulate cell size and protein content at Start, it is proposed that both extracellular and intracellular glucose signalling is required for properly setting the cell sizer in glucose media.

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Suzuki, Chizuko, Hiroshi Nagasaki, Yoshiki Okajima, Hidetaka Suga, Hiroshi Arima, Yasumasa Iwasaki, and Yutaka Oiso. "The LIM domain homeobox gene isl-1 is a positive regulator of glycoprotein alpha 2 (GPA2), a subunit of thyrostimulin." Regulatory Peptides 142, no. 1-2 (July 2007): 60–67. http://dx.doi.org/10.1016/j.regpep.2007.01.009.

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Journal articles on the topic 'Gpa2'

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