Gene Symbol: PDE2
Description: 3',5'-cyclic-nucleotide phosphodiesterase PDE2
Alias: SRA5, 3',5'-cyclic-nucleotide phosphodiesterase PDE2
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Peeters T, Louwet W, Geladé R, Nauwelaers D, Thevelein J, Versele M. Kelch-repeat proteins interacting with the Galpha protein Gpa2 bypass adenylate cyclase for direct regulation of protein kinase A in yeast. Proc Natl Acad Sci U S A. 2006;103:13034-9 pubmed
    ..Importantly, we show that Krh1/2 also enhance the association between mouse R and C subunits, suggesting that Krh control of PKA has been evolutionarily conserved. ..
  2. Li J, Li Y, Elledge S. Genetic analysis of the kinetochore DASH complex reveals an antagonistic relationship with the ras/protein kinase A pathway and a novel subunit required for Ask1 association. Mol Cell Biol. 2005;25:767-78 pubmed
    ..Overexpression of PDE2 or deletion of RAS2 rescued the temperature sensitivity of ask1-3 mutants...
  3. Nikawa J, Sass P, Wigler M. Cloning and characterization of the low-affinity cyclic AMP phosphodiesterase gene of Saccharomyces cerevisiae. Mol Cell Biol. 1987;7:3629-36 pubmed
    ..We previously isolated and characterized PDE2, which encodes a high-affinity cAMP phosphodiesterase. We have now isolated the PDE1 gene of S...
  4. Sass P, Field J, Nikawa J, Toda T, Wigler M. Cloning and characterization of the high-affinity cAMP phosphodiesterase of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1986;83:9303-7 pubmed
    A gene, PDE2, has been cloned from the yeast Saccharomyces cerevisiae that, when present in high copy, reverses the phenotypic effects of RAS2Val19, a mutant form of the RAS2 gene that renders yeast cells sensitive to heat shock and ..
  5. Irniger S, Baumer M, Braus G. Glucose and ras activity influence the ubiquitin ligases APC/C and SCF in Saccharomyces cerevisiae. Genetics. 2000;154:1509-21 pubmed
    ..by reduced Ras signaling activity, by a deletion of the RAS2 gene, by a cdc25 mutation, by elevated levels of PDE2, or by growth without glucose. Viability of these mutants is also enhanced by decreased Cdk1 activity...
  6. Wilson R, Renault G, Jacquet M, Tatchell K. The pde2 gene of Saccharomyces cerevisiae is allelic to rca1 and encodes a phosphodiesterase which protects the cell from extracellular cAMP. FEBS Lett. 1993;325:191-5 pubmed
    The high affinity cAMP phosphodiesterase, encoded by PDE2, is an important component of the cAMP-dependent protein kinase signaling system in Saccharomyces cerevisiae...
  7. Anghileri P, Branduardi P, Sternieri F, Monti P, Visintin R, Bevilacqua A, et al. Chromosome separation and exit from mitosis in budding yeast: dependence on growth revealed by cAMP-mediated inhibition. Exp Cell Res. 1999;250:510-23 pubmed
    ..A possible functional antagonism between PKAs and the mitosis promoting factor is also discussed. ..
  8. Gourlay C, Ayscough K. Identification of an upstream regulatory pathway controlling actin-mediated apoptosis in yeast. J Cell Sci. 2005;118:2119-32 pubmed
    ..We also demonstrate that overexpression of PDE2, a negative regulator of the Ras/cAMP pathway rescues actin dynamics, reduces oxidative stress sensitivity and ..
  9. Leadsham J, Miller K, Ayscough K, Colombo S, Martegani E, Sudbery P, et al. Whi2p links nutritional sensing to actin-dependent Ras-cAMP-PKA regulation and apoptosis in yeast. J Cell Sci. 2009;122:706-15 pubmed publisher
    ..We also demonstrate for the first time that Whi2p-dependent regulation of cAMP-PKA signalling plays a physiological role in the differentiation of yeast colonies by facilitating elaboration of distinct zones of cell death. ..

More Information


  1. Trott A, Shaner L, Morano K. The molecular chaperone Sse1 and the growth control protein kinase Sch9 collaborate to regulate protein kinase A activity in Saccharomyces cerevisiae. Genetics. 2005;170:1009-21 pubmed
    ..Together these results demonstrate that the Sse1 chaperone and the growth control kinase Sch9 independently contribute to regulation of PKA signaling. ..
  2. Heo S, Tatebayashi K, Ikeda H. The budding yeast cohesin gene SCC1/MCD1/RHC21 genetically interacts with PKA, CDK and APC. Curr Genet. 1999;36:329-38 pubmed
    ..Firstly, PDE2 and BCY1, each of which inhibits the activity of protein kinase A (PKA), suppressed the temperature sensitivity of ..
  3. Ma P, Wera S, Van Dijck P, Thevelein J. The PDE1-encoded low-affinity phosphodiesterase in the yeast Saccharomyces cerevisiae has a specific function in controlling agonist-induced cAMP signaling. Mol Biol Cell. 1999;10:91-104 pubmed
    The yeast Saccharomyces cerevisiae contains two genes, PDE1 and PDE2, which respectively encode a low-affinity and a high-affinity cAMP phosphodiesterase. The physiological function of the low-affinity enzyme Pde1 is unclear...
  4. Casado C, González A, Platara M, Ruiz A, Arino J. The role of the protein kinase A pathway in the response to alkaline pH stress in yeast. Biochem J. 2011;438:523-33 pubmed publisher
    ..However, the relevance of attenuation of PKA in high pH tolerance is probably not restricted to regulation of Msn2 function. ..
  5. Park J, Collinson E, Grant C, Dawes I. Rom2p, the Rho1 GTP/GDP exchange factor of Saccharomyces cerevisiae, can mediate stress responses via the Ras-cAMP pathway. J Biol Chem. 2005;280:2529-35 pubmed
  6. Howard S, Budovskaya Y, Chang Y, Herman P. The C-terminal domain of the largest subunit of RNA polymerase II is required for stationary phase entry and functionally interacts with the Ras/PKA signaling pathway. J Biol Chem. 2002;277:19488-97 pubmed
    ..In all, these data suggested that S. cerevisiae growth control and RNA pol II transcription might be coupled by using the Ras pathway to regulate CTD function. ..
  7. Costigan C, Snyder M. SLK1, a yeast homolog of MAP kinase activators, has a RAS/cAMP-independent role in nutrient sensing. Mol Gen Genet. 1994;243:286-96 pubmed
    ..Combining the slk1-delta mutation with a mutation that is thought constitutively activate the PKA pathway, pde2, resulted in enhanced growth control defects...
  8. Gitler A, Chesi A, Geddie M, Strathearn K, Hamamichi S, Hill K, et al. Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. Nat Genet. 2009;41:308-15 pubmed publisher
    ..Finally, we show that additional genes from our yeast screen, with diverse functions, are potent modifiers of alpha-syn-induced neuron loss in animals, establishing a diverse, highly conserved interaction network for alpha-syn. ..
  9. Zhu X, Démolis N, Jacquet M, Michaeli T. MSI1 suppresses hyperactive RAS via the cAMP-dependent protein kinase and independently of chromatin assembly factor-1. Curr Genet. 2000;38:60-70 pubmed
    ..MSI1 appears to provide two distinct roles in chromatin modeling as a component of yCAF-1, and in the inhibition of RAS signaling by modulating PKA. ..
  10. Hu Y, Liu E, Bai X, Zhang A. The localization and concentration of the PDE2-encoded high-affinity cAMP phosphodiesterase is regulated by cAMP-dependent protein kinase A in the yeast Saccharomyces cerevisiae. FEMS Yeast Res. 2010;10:177-87 pubmed publisher
    ..cerevisiae encodes two cyclic AMP (cAMP) phosphodiesterases, a low-affinity one, Pde1, and a high-affinity one, Pde2. Pde1 has been ascribed a function for downregulating agonist-induced cAMP accumulation in a protein kinase A (PKA)-..
  11. Colicelli J, Nicolette C, Birchmeier C, Rodgers L, Riggs M, Wigler M. Expression of three mammalian cDNAs that interfere with RAS function in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1991;88:2913-7 pubmed
    ..cerevisiae strains expressing the activated RAS2Val19 gene or lacking both cAMP phosphodiesterase genes, PDE1 and PDE2, have impaired growth control and display an acute sensitivity to heat shock...
  12. Park J, Grant C, Dawes I. The high-affinity cAMP phosphodiesterase of Saccharomyces cerevisiae is the major determinant of cAMP levels in stationary phase: involvement of different branches of the Ras-cyclic AMP pathway in stress responses. Biochem Biophys Res Commun. 2005;327:311-9 pubmed
    ..on the separate branch of the Ras-cAMP pathway, the low- or high-affinity cAMP phosphodiesterase encoded by PDE1 or PDE2, respectively...
  13. Oki M, Nishimoto T. A protein required for nuclear-protein import, Mog1p, directly interacts with GTP-Gsp1p, the Saccharomyces cerevisiae ran homologue. Proc Natl Acad Sci U S A. 1998;95:15388-93 pubmed
    ..We report here isolation of three multicopy suppressors-PDE2, NTF2, and a gene designated MOG1-all of which rescued a growth defect of these gsp1 strains...
  14. Imazu H, Sakurai H. Saccharomyces cerevisiae heat shock transcription factor regulates cell wall remodeling in response to heat shock. Eukaryot Cell. 2005;4:1050-6 pubmed
    ..Several of the other suppressors were found to encode proteins functioning in cell wall organization. These results suggest that Hsf1 in concert with Pkc1 regulates cell wall remodeling in response to heat shock. ..
  15. Mitsuzawa H. Responsiveness to exogenous cAMP of a Saccharomyces cerevisiae strain conferred by naturally occurring alleles of PDE1 and PDE2. Genetics. 1993;135:321-6 pubmed
    ..revealed that the responsiveness to cAMP results from naturally occurring loss-of-function alleles of PDE1 and PDE2, which encode low and high affinity cAMP phosphodiesterases, respectively...
  16. Wang Z, Wilson W, Fujino M, Roach P. Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p. Mol Cell Biol. 2001;21:5742-52 pubmed
    ..Defective glycogen storage in snf1 cells can be attributed to both defective synthesis upon entry into stationary phase and impaired maintenance of glycogen levels caused by the lack of autophagy. ..
  17. Noubhani A, Bunoust O, Bonini B, Thevelein J, Devin A, Rigoulet M. The trehalose pathway regulates mitochondrial respiratory chain content through hexokinase 2 and cAMP in Saccharomyces cerevisiae. J Biol Chem. 2009;284:27229-34 pubmed publisher
    ..This is the first time that a pathway involved in sugar storage, i.e. trehalose, is shown to regulate the mitochondrial enzymatic content. ..
  18. Roosen J, Engelen K, Marchal K, Mathys J, Griffioen G, Cameroni E, et al. PKA and Sch9 control a molecular switch important for the proper adaptation to nutrient availability. Mol Microbiol. 2005;55:862-80 pubmed
    ..This mechanism allows fine-tuning various nutritional responses in yeast cells, allowing them to adapt metabolism and growth appropriately. ..
  19. Leadsham J, Gourlay C. cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation. BMC Cell Biol. 2010;11:92 pubmed publisher
    ..The visualization of cAMP/TPK3 induced cell death within yeast colonies supports a model that PKA regulation plays a physiological role in coordinating respiratory function and cell death with nutritional status in budding yeast. ..
  20. Favot L, Keravis T, Lugnier C. Modulation of VEGF-induced endothelial cell cycle protein expression through cyclic AMP hydrolysis by PDE2 and PDE4. Thromb Haemost. 2004;92:634-45 pubmed
    ..The role of PDE2 and PDE4 in VEGF-induced proliferation in HUVEC was investigated: 1) VEGF increased cAMP-hydrolytic activity by up-..
  21. Sasaki T, Toh e A, Kikuchi Y. Extragenic suppressors that rescue defects in the heat stress response of the budding yeast mutant tom1. Mol Gen Genet. 2000;262:940-8 pubmed
    ..It was found that the temperature sensitivity of the tom1-2 mutant is indeed suppressed by multiple copies of PDE2 or BCY1, which encode negative regulators of the cAMP/PKA pathway...
  22. Tohe A, Oguchi T. Isolation and characterization of the yeast las21 mutants, which are sensitive to a local anestheticum, tetracaine. Genes Genet Syst. 1998;73:365-75 pubmed
    ..We found some genetic interactions between LAS21 and Ras/cAMP cascade genes. These results suggest that LAS21 defines unknown pathway regulating the stress response of yeast. ..
  23. Harkness T, Shea K, Legrand C, Brahmania M, Davies G. A functional analysis reveals dependence on the anaphase-promoting complex for prolonged life span in yeast. Genetics. 2004;168:759-74 pubmed
    ..Multicopy expression of genes encoding Snf1p (MIG1) and PKA (PDE2) aging-pathway components suppressed apc5CA phenotypes, suggesting their involvement in APC-dependent longevity...
  24. Ma L, Ho K, Piggott N, Luo Z, Measday V. Interactions between the kinetochore complex and the protein kinase A pathway in Saccharomyces cerevisiae. G3 (Bethesda). 2012;2:831-41 pubmed publisher
    ..Overall, our data suggest that the increased protein kinase A activity in kinetochore mutants is detrimental to cellular growth and chromosome transmission fidelity. ..
  25. Balciunas D, Ronne H. Yeast genes GIS1-4: multicopy suppressors of the Gal- phenotype of snf1 mig1 srb8/10/11 cells. Mol Gen Genet. 1999;262:589-99 pubmed
    ..GIS5-7 are identical to the previously described genes PDE2, SGE1 and TUB3, respectively. None of the suppressor genes seem to be involved in Mediator function...
  26. Poplinski A, Hopp C, Ramezani Rad M. Ste50 adaptor protein influences Ras/cAMP-driven stress-response and cell survival in Saccharomyces cerevisiae. Curr Genet. 2007;51:257-68 pubmed
    ..highly activated Ras-cyclic AMP (cAMP) pathway by deletion of the high-affinity cAMP-dependent phosphodiesterase 2 (PDE2) leads to repression of a stress mediated response and cell survival...
  27. Li Y, Wang Y. Ras protein/cAMP-dependent protein kinase signaling is negatively regulated by a deubiquitinating enzyme, Ubp3, in yeast. J Biol Chem. 2013;288:11358-65 pubmed publisher
    ..that the increased cAMP is responsible for the abnormal signaling behavior of the ubp3? mutant, overexpressing PDE2, which encodes a phosphodiesterase that hydrolyzes cAMP, significantly relieves the cell size increase and heat ..
  28. Avrahami Moyal L, Braun S, Engelberg D. Overexpression of PDE2 or SSD1-V in Saccharomyces cerevisiae W303-1A strain renders it ethanol-tolerant. FEMS Yeast Res. 2012;12:447-55 pubmed publisher
    ..Two genomic fragments from this library rescued the ethanol sensitivity of W303-1A. One contained the PDE2 gene, which when over-expressed, conferred ethanol tolerance...
  29. Drobna E, Gazdag Z, Culakova H, Dzugasova V, Gbelska Y, Pesti M, et al. Overexpression of the YAP1, PDE2, and STB3 genes enhances the tolerance of yeast to oxidative stress induced by 7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine. FEMS Yeast Res. 2012;12:958-68 pubmed publisher
    ..screening of Saccharomyces cerevisiae genomic library in the high-copy-number plasmid revealed three genes, YAP1, PDE2, and STB3, which increased the CTBT tolerance of the parental strain...
  30. Niles B, Joslin A, Fresques T, Powers T. TOR complex 2-Ypk1 signaling maintains sphingolipid homeostasis by sensing and regulating ROS accumulation. Cell Rep. 2014;6:541-52 pubmed publisher
    ..Thus, ROS sensing and signaling by TORC2/Ypk1 play a central physiological role in sphingolipid biosynthesis and in the maintenance of cell growth and viability. ..
  31. Hubbard E, Yang X, Carlson M. Relationship of the cAMP-dependent protein kinase pathway to the SNF1 protein kinase and invertase expression in Saccharomyces cerevisiae. Genetics. 1992;130:71-80 pubmed
    ..Among the nine genes recovered were two genes from the cAMP-dependent protein kinase (cAPK) pathway, MSI1 and PDE2. Increased dosage of these genes partially compensates for defects in nutrient utilization and sporulation in snf1 ..
  32. Kang W, Devare M, Kim J. HST1 increases replicative lifespan of a sir2? mutant in the absence of PDE2 in Saccharomyces cerevisiae. J Microbiol. 2017;55:123-129 pubmed publisher
    ..deacetylates the acetylated lysine 16 of histone H4 (H4K16Ac) and represses PMA1 transcription in the sir2? pde2? mutant. We further show that Hst1 plays a role in extending the RLS of the sir2? pde2? mutant...
  33. Chavel C, Dionne H, Birkaya B, Joshi J, Cullen P. Multiple signals converge on a differentiation MAPK pathway. PLoS Genet. 2010;6:e1000883 pubmed publisher
    ..Systems-level integration of signaling circuitry is likely to coordinate other regulatory networks that control complex behaviors. ..
  34. Wilson R, Tatchell K. SRA5 encodes the low-Km cyclic AMP phosphodiesterase of Saccharomyces cerevisiae. Mol Cell Biol. 1988;8:505-10 pubmed
    ..It maps to the right arm of chromosome XV, tightly linked to PRT1, and its sequence matches the sequence of PDE2, encoding the low-Km cAMP phosphodiesterase...
  35. Garrett S, Broach J. Loss of Ras activity in Saccharomyces cerevisiae is suppressed by disruptions of a new kinase gene, YAKI, whose product may act downstream of the cAMP-dependent protein kinase. Genes Dev. 1989;3:1336-48 pubmed
    ..Finally, the coding region predicts a protein with significant homology to the family of protein kinases, suggesting that loss of cAMP-dependent protein kinase function can be suppressed by the loss of a second protein kinase. ..
  36. Sobering A, Jung U, Lee K, Levin D. Yeast Rpi1 is a putative transcriptional regulator that contributes to preparation for stationary phase. Eukaryot Cell. 2002;1:56-65 pubmed
    ..Finally, we propose that inappropriate expression of RPI1 during log phase growth drives fortification of the cell wall and that this behavior is responsible for suppression of the mpkl cell lysis defect. ..
  37. Tomlin G, Hamilton G, Gardner D, Walmsley R, Stateva L, Oliver S. Suppression of sorbitol dependence in a strain bearing a mutation in the SRB1/PSA1/VIG9 gene encoding GDP-mannose pyrophosphorylase by PDE2 overexpression suggests a role for the Ras/cAMP signal-transduction pathway in the control of yeast cell-wall . Microbiology. 2000;146 ( Pt 9):2133-46 pubmed
    ..A previously reported complementing gene, which this study has now identified as PDE2, is a multi-copy suppressor of sorbitol dependence and is not, as was previously suggested, the SRB1 gene...
  38. Matsuura A, Anraku Y. Genetic interaction between the Ras-cAMP pathway and the Dis2s1/Glc7 protein phosphatase in Saccharomyces cerevisiae. Mol Gen Genet. 1994;242:257-62 pubmed
    ..Furthermore, the dis2s1ts mutation was shown to be suppressed by a multicopy plasmid harboring PDE2, a gene for cAMP phosphodiesterase...
  39. Lesuisse E, Horion B, Labbe P, Hilger F. The plasma membrane ferrireductase activity of Saccharomyces cerevisiae is partially controlled by cyclic AMP. Biochem J. 1991;280 ( Pt 2):545-8 pubmed
    ..This drop was prevented in the double mutant cdc35 sra5 by adding cyclic AMP to the growth medium...