The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PDE2  -  3',5'-cyclic-nucleotide phosphodiesterase...

Saccharomyces cerevisiae S288c

Synonyms: 3',5'-cyclic-nucleotide phosphodiesterase 2, High-affinity cAMP phosphodiesterase, PDEase 2, SRA5, YOR360C
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PDE2

  • The effect of the oncogenic RAS allele on the replicative life-span is primarily asserted via the PKA-dependent pathway since Pde2p, but not UCP1, overproduction suppressed premature aging of the RAS2(val19) mutant [1].

High impact information on PDE2

  • Previous studies have implicated GPA2 in the control of intracellular cAMP levels; we find that expression of the dominant RAS2(Gly19Val) mutant or exogenous cAMP suppresses the Deltagpa2 pseudohyphal defect. cAMP also stimulates filamentation in strains lacking the cAMP phosphodiesterase PDE2, even in the absence of nitrogen starvation [2].
  • Furthermore, the finding that PDE2 suppressed both gsp1 and rna1-1 indicates that the Ran GTPase cycle is regulated by the Ras-cAMP pathway [3].
  • Saccharomyces 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 [4].
  • 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 starvation [5].
  • We report here that PDE2 encodes a high-affinity cAMP phosphodiesterase that shares sequence homology with animal cell phosphodiesterases [5].

Biological context of PDE2

  • High-copy-number plasmids containing either PDE1 or PDE2 can reverse the growth arrest defects of yeast cells carrying the RAS2(Val-19) mutation [6].
  • Both of these phenotypes can be rescued by deletion of the PDE2 gene product, which inactivates cAMP by cleavage, suggesting that these phenotypes can be attributed to low levels of intracellular cAMP [7].
  • 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 [8].
  • When PKA activity was low (in the presence of multicopy PDE2 or a cyr1(D822-->A) mutation) maximum reporter gene activity was observed even in the absence of oxidative stress [9].
  • Its catalytic domain exhibits 30-40% sequence identity with those of all 11 mammalian phosphodiesterase (PDE) families, as well as with PDE2 from Saccharomyces cerevisiae, dunce from Drosophila melanogaster, and regA from Dictyostelium discoideum [10].

Anatomical context of PDE2


Associations of PDE2 with chemical compounds

  • Deletion of PDE2, similar to ira2 deletion, rendered cells sensitive to freeze-thawing, peroxides, paraquat, cycloheximide, heavy metals, NaCl, heat, or cold shock [12].
  • We show that deletion of PDE1, but not PDE2, results in a much higher cAMP accumulation upon addition of glucose or upon intracellular acidification [13].
  • However, the hac1 disruptant becomes caffeine sensitive, which is suppressed by multicopy expression of the yeast PDE2 (Phosphodiesterase 2) gene [14].
  • Three of the six RAS2Val19 suppressors could suppress the deletion of PDE1 and PDE2, the cAMP phosphodiesterase (Pde)-encoding genes, suggesting that they act downstream from adenylyl cyclase (Cyr) [15].
  • This activity was inhibited by EHNA, a selective PDE2 inhibitor, and was stimulated three-fold by cGMP [16].

Regulatory relationships of PDE2


Other interactions of PDE2


  1. The oncogenic RAS2(val19) mutation locks respiration, independently of PKA, in a mode prone to generate ROS. Hlavatá, L., Aguilaniu, H., Pichová, A., Nyström, T. EMBO J. (2003) [Pubmed]
  2. Yeast pseudohyphal growth is regulated by GPA2, a G protein alpha homolog. Lorenz, M.C., Heitman, J. EMBO J. (1997) [Pubmed]
  3. A protein required for nuclear-protein import, Mog1p, directly interacts with GTP-Gsp1p, the Saccharomyces cerevisiae ran homologue. Oki, M., Nishimoto, T. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Expression of three mammalian cDNAs that interfere with RAS function in Saccharomyces cerevisiae. Colicelli, J., Nicolette, C., Birchmeier, C., Rodgers, L., Riggs, M., Wigler, M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  5. Cloning and characterization of the high-affinity cAMP phosphodiesterase of Saccharomyces cerevisiae. Sass, P., Field, J., Nikawa, J., Toda, T., Wigler, M. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  6. Cloning and characterization of the low-affinity cyclic AMP phosphodiesterase gene of Saccharomyces cerevisiae. Nikawa, J., Sass, P., Wigler, M. Mol. Cell. Biol. (1987) [Pubmed]
  7. Gpa2p, a G-protein alpha-subunit, regulates growth and pseudohyphal development in Saccharomyces cerevisiae via a cAMP-dependent mechanism. Kübler, E., Mösch, H.U., Rupp, S., Lisanti, M.P. J. Biol. Chem. (1997) [Pubmed]
  8. SRA5 encodes the low-Km cyclic AMP phosphodiesterase of Saccharomyces cerevisiae. Wilson, R.B., Tatchell, K. Mol. Cell. Biol. (1988) [Pubmed]
  9. The oxidative stress response mediated via Pos9/Skn7 is negatively regulated by the Ras/PKA pathway in Saccharomyces cerevisiae. Charizanis, C., Juhnke, H., Krems, B., Entian, K.D. Mol. Gen. Genet. (1999) [Pubmed]
  10. Characterization of TbPDE2A, a novel cyclic nucleotide-specific phosphodiesterase from the protozoan parasite Trypanosoma brucei. Zoraghi, R., Kunz, S., Gong, K., Seebeck, T. J. Biol. Chem. (2001) [Pubmed]
  11. Deletion of PDE2, the gene encoding the high-affinity cAMP phosphodiesterase, results in changes of the cell wall and membrane in Candida albicans. Jung, W.H., Warn, P., Ragni, E., Popolo, L., Nunn, C.D., Turner, M.P., Stateva, L. Yeast (2005) [Pubmed]
  12. 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. Park, J.I., Grant, C.M., Dawes, I.W. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  13. The PDE1-encoded low-affinity phosphodiesterase in the yeast Saccharomyces cerevisiae has a specific function in controlling agonist-induced cAMP signaling. Ma, P., Wera, S., Van Dijck, P., Thevelein, J.M. Mol. Biol. Cell (1999) [Pubmed]
  14. Hac1: a novel yeast bZIP protein binding to the CRE motif is a multicopy suppressor for cdc10 mutant of Schizosaccharomyces pombe. Nojima, H., Leem, S.H., Araki, H., Sakai, A., Nakashima, N., Kanaoka, Y., Ono, Y. Nucleic Acids Res. (1994) [Pubmed]
  15. Identification and genetic analysis of Schizosaccharomyces pombe cDNAs that suppress deletion of IRA1 in Saccharomyces cerevisiae. Matviw, H., Yu, G., Young, D. Gene (1993) [Pubmed]
  16. Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase. Rosman, G.J., Martins, T.J., Sonnenburg, W.K., Beavo, J.A., Ferguson, K., Loughney, K. Gene (1997) [Pubmed]
  17. Rom2p, the Rho1 GTP/GDP exchange factor of Saccharomyces cerevisiae, can mediate stress responses via the Ras-cAMP pathway. Park, J.I., Collinson, E.J., Grant, C.M., Dawes, I.W. J. Biol. Chem. (2005) [Pubmed]
  18. Relationship of the cAMP-dependent protein kinase pathway to the SNF1 protein kinase and invertase expression in Saccharomyces cerevisiae. Hubbard, E.J., Yang, X.L., Carlson, M. Genetics (1992) [Pubmed]
  19. Analysis of the mechanism of activation of cAMP-dependent protein kinase through the study of mutants of the yeast regulatory subunit. Zaremberg, V., Moreno, S. Eur. J. Biochem. (1996) [Pubmed]
  20. Ssa1p chaperone interacts with the guanine nucleotide exchange factor of ras Cdc25p and controls the cAMP pathway in Saccharomyces cerevisiae. Geymonat, M., Wang, L., Garreau, H., Jacquet, M. Mol. Microbiol. (1998) [Pubmed]
WikiGenes - Universities