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Gene Review

BCY1  -  cAMP-dependent protein kinase regulatory...

Saccharomyces cerevisiae S288c

Synonyms: Bypass of cyclase mutations protein 1, PKA regulatory subunit, Protein kinase A regulatory subunit, REG1, SRA1, ...
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Disease relevance of BCY1


High impact information on BCY1

  • We have isolated mutant TPK genes that suppress all of the bcy1- defects [3].
  • S. cerevisiae strains containing RAS2val19, a RAS2 gene with a missense mutation analogous to one that activates the transforming potential of mammalian ras genes, have growth and biochemical properties strikingly similar to yeast strains carrying IAC or bcy1 [4].
  • Yeast strains carrying the IAC mutation have elevated levels of adenylate cyclase activity. bcy1 is a mutation that suppresses the lethality in adenylate cyclase deficient yeast [4].
  • In diploids homozygous for the bcy1 mutation that results in deficiency of the regulatory subunit of cAMP-dependent protein kinase and production of a high level of the catalytic subunit of this enzyme, no premeiotic DNA replication and commitment to intragenic recombination occurred, and no spores were formed [5].
  • A strain with a mutation in the regulatory subunit of the cAMP-dependent protein kinase (bcy1) fails to accumulate GPH1 and GAC1 RNA [6].

Biological context of BCY1

  • The cellular level of C1 was increased by expressing the genes for C1 (TPK1) and yeast regulatory subunit (BCY1) on multiple copy plasmids within this strain [7].
  • In contrast, a mutation in RAS2 (RAS2val19) which increases the level of cAMP or a mutation in the regulatory subunit (BCY1) of cAMP-dependent protein kinase which results in unregulated cAMP-dependent protein kinase activity accentuates the snf1 phenotype [8].
  • Spontaneous mutations in the gene which encodes the regulatory subunit of cAMP-dependent protein kinase (PKA) of Saccharomyces cerevisiae (BCY1) have been isolated previously [Cannon, J. F., Gibbs, J. B. & Tatchell, K. (1986) Genetics 113, 247-264] by selection of ras2::LEU2 revertants that grew on non-fermentable carbon sources [9].
  • The presence in a bcy1 diploid of IME1 multicopy plasmids does not cure the failure of bcy1 cells to arrest as unbudded cells following starvation and to enter the G0 state (thermotolerance, synthesis of unique G0 proteins) [10].
  • We cloned SRA1 and SRA3 and determined their DNA sequences [11].

Anatomical context of BCY1

  • Remarkably, Zds1 appears to act as a negative regulator of cell wall integrity signaling, and this activity is dependent in part on the phosphorylation status of Bcy1 [12].
  • Furthermore, the treatment of membranes with cAMP or dibutyryl cAMP caused the activation of PI kinase in wild type, ras1, cry1-2, and ras2 strains, but not in bcy1 strain cells [13].
  • By using photoaffinity labeling with 8-N3-[32P]cAMP, we have identified in plasma membrane vesicles a cAMP-binding protein (Mr = 54,000) that is present also in bcy1 disruption mutants, lacking the cytoplasmic R subunit of protein kinase A (PKA) [14].

Associations of BCY1 with chemical compounds

  • Yeast transformants containing increased kinase activity resulting from overexpression of RAS2Val19 or TPK1 and yeast strains having increased kinase activities due to mutations in the BCY1 gene also did not show alterations in their sensitivity to cisplatin [15].
  • In the bcy1 tpk2 mutant, protein kinase A activity (due to the presence of the TPK1 gene) was cyclic AMP independent, indicating that the cells harbored an unregulated phosphotransferase activity [16].
  • The morphogenetic behavior of several C. albicans mutant strains bearing one or both BCY1 alleles, in a wild-type and in a TPK2 null genetic background, was assessed in N-acetylglucosamine (GlcNAc) liquid medium at 37 degrees C. Strains with one BCY1 allele tagged or not, behaved similarly, displaying pseudohyphae and true hyphae [17].
  • In glucose-grown cells, Bcy1 is almost exclusively nuclear, while it appears more evenly distributed between nucleus and cytoplasm in carbon source-derepressed cells [18].
  • Site-directed mutagenesis of two clusters (I and II) of serines near the N terminus to alanine resulted in an enhanced nuclear accumulation of Bcy1 in ethanol-grown cells [18].

Physical interactions of BCY1


Enzymatic interactions of BCY1


Regulatory relationships of BCY1

  • In addition, we have identified a polymorphic gene, SSD1, that in some versions can suppress the lethality due to a deletion of SIT4 and can also partially suppress the phenotypic defects due to a null mutation in BCY1 [21].
  • Furthermore, a deficiency of the cAMP-binding regulatory subunit (RA) caused by the bcy1 mutation fails to suppress the cdc25 mutation, indicating that PK-25 does not interact with the cAMP receptor protein [22].
  • The multicopy MSI2 also suppresses the heat shock sensitivity of cells with the RAS2val19 mutation but not those with the bcy1 mutation, suggesting that the MSI2 protein may interfere with the activity of the RAS protein [23].
  • In Saccharomyces cerevisiae, the unregulated cyclic AMP-dependent protein kinase (cAPK) activity of bcy1 mutant cells inhibits expression of the glucose-repressible ADH2 gene [24].
  • Previous studies showed that Reg1 regulates the Snf1 protein kinase in response to glucose [19].

Other interactions of BCY1


Analytical, diagnostic and therapeutic context of BCY1


  1. Expression in Escherichia coli of BCY1, the regulatory subunit of cyclic AMP-dependent protein kinase from Saccharomyces cerevisiae. Purification and characterization. Johnson, K.E., Cameron, S., Toda, T., Wigler, M., Zoller, M.J. J. Biol. Chem. (1987) [Pubmed]
  2. Deletion of BCY1 from the Saccharomyces cerevisiae genome is semidominant and induces autolytic phenotypes suitable for improvement of sparkling wines. Tabera, L., Muñoz, R., Gonzalez, R. Appl. Environ. Microbiol. (2006) [Pubmed]
  3. cAMP-independent control of sporulation, glycogen metabolism, and heat shock resistance in S. cerevisiae. Cameron, S., Levin, L., Zoller, M., Wigler, M. Cell (1988) [Pubmed]
  4. In yeast, RAS proteins are controlling elements of adenylate cyclase. Toda, T., Uno, I., Ishikawa, T., Powers, S., Kataoka, T., Broek, D., Cameron, S., Broach, J., Matsumoto, K., Wigler, M. Cell (1985) [Pubmed]
  5. Initiation of meiosis in yeast mutants defective in adenylate cyclase and cyclic AMP-dependent protein kinase. Matsumoto, K., Uno, I., Ishikawa, T. Cell (1983) [Pubmed]
  6. GAC1 may encode a regulatory subunit for protein phosphatase type 1 in Saccharomyces cerevisiae. François, J.M., Thompson-Jaeger, S., Skroch, J., Zellenka, U., Spevak, W., Tatchell, K. EMBO J. (1992) [Pubmed]
  7. Purification and characterization of C1, the catalytic subunit of Saccharomyces cerevisiae cAMP-dependent protein kinase encoded by TPK1. Zoller, M.J., Kuret, J., Cameron, S., Levin, L., Johnson, K.E. J. Biol. Chem. (1988) [Pubmed]
  8. Deletion of SNF1 affects the nutrient response of yeast and resembles mutations which activate the adenylate cyclase pathway. Thompson-Jaeger, S., François, J., Gaughran, J.P., Tatchell, K. Genetics (1991) [Pubmed]
  9. 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]
  10. The adenylate cyclase/protein kinase cascade regulates entry into meiosis in Saccharomyces cerevisiae through the gene IME1. Matsuura, A., Treinin, M., Mitsuzawa, H., Kassir, Y., Uno, I., Simchen, G. EMBO J. (1990) [Pubmed]
  11. Characterization of Saccharomyces cerevisiae genes encoding subunits of cyclic AMP-dependent protein kinase. Cannon, J.F., Tatchell, K. Mol. Cell. Biol. (1987) [Pubmed]
  12. Feedback inhibition on cell wall integrity signaling by Zds1 involves Gsk3 phosphorylation of a cAMP-dependent protein kinase regulatory subunit. Griffioen, G., Swinnen, S., Thevelein, J.M. J. Biol. Chem. (2003) [Pubmed]
  13. Activation of phosphatidylinositol kinase and phosphatidylinositol-4-phosphate kinase by cAMP in Saccharomyces cerevisiae. Kato, H., Uno, I., Ishikawa, T., Takenawa, T. J. Biol. Chem. (1989) [Pubmed]
  14. A cAMP-binding ectoprotein in the yeast Saccharomyces cerevisiae. Müller, G., Bandlow, W. Biochemistry (1991) [Pubmed]
  15. Cisplatin sensitivity in cAMP-dependent protein kinase mutants of Saccharomyces cerevisiae. Cvijic, M.E., Yang, W.L., Chin, K.V. Anticancer Res. (1998) [Pubmed]
  16. Candida albicans lacking the gene encoding the regulatory subunit of protein kinase A displays a defect in hyphal formation and an altered localization of the catalytic subunit. Cassola, A., Parrot, M., Silberstein, S., Magee, B.B., Passeron, S., Giasson, L., Cantore, M.L. Eukaryotic Cell (2004) [Pubmed]
  17. Expression levels and subcellular localization of Bcy1p in Candida albicans mutant strains devoid of one BCY1 allele results in a defective morphogenetic behavior. Giacometti, R., Souto, G., Silberstein, S., Giasson, L., Cantore, M.L., Passeron, S. Biochim. Biophys. Acta (2006) [Pubmed]
  18. Nucleocytoplasmic distribution of budding yeast protein kinase A regulatory subunit Bcy1 requires Zds1 and is regulated by Yak1-dependent phosphorylation of its targeting domain. Griffioen, G., Branduardi, P., Ballarini, A., Anghileri, P., Norbeck, J., Baroni, M.D., Ruis, H. Mol. Cell. Biol. (2001) [Pubmed]
  19. Regulatory interactions between the Reg1-Glc7 protein phosphatase and the Snf1 protein kinase. Sanz, P., Alms, G.R., Haystead, T.A., Carlson, M. Mol. Cell. Biol. (2000) [Pubmed]
  20. Phosphorylation of yeast phosphatidylserine synthase in vivo and in vitro by cyclic AMP-dependent protein kinase. Kinney, A.J., Carman, G.M. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  21. The SIT4 protein phosphatase functions in late G1 for progression into S phase. Sutton, A., Immanuel, D., Arndt, K.T. Mol. Cell. Biol. (1991) [Pubmed]
  22. Isolation and nucleotide sequence of a Saccharomyces cerevisiae protein kinase gene suppressing the cell cycle start mutation cdc25. Lisziewicz, J., Godany, A., Förster, H.H., Küntzel, H. J. Biol. Chem. (1987) [Pubmed]
  23. Isolation of a CDC25 family gene, MSI2/LTE1, as a multicopy suppressor of ira1. Shirayama, M., Matsui, Y., Tanaka, K., Toh-e, A. Yeast (1994) [Pubmed]
  24. Cyclic AMP-dependent protein kinase inhibits ADH2 expression in part by decreasing expression of the transcription factor gene ADR1. Dombek, K.M., Young, E.T. Mol. Cell. Biol. (1997) [Pubmed]
  25. Suppressors of the ras2 mutation of Saccharomyces cerevisiae. Cannon, J.F., Gibbs, J.B., Tatchell, K. Genetics (1986) [Pubmed]
  26. Low activity of the yeast cAMP-dependent protein kinase catalytic subunit Tpk3 is due to the poor expression of the TPK3 gene. Mazón, M.J., Behrens, M.M., Morgado, E., Portillo, F. Eur. J. Biochem. (1993) [Pubmed]
  27. 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. Li, J.M., Li, Y., Elledge, S.J. Mol. Cell. Biol. (2005) [Pubmed]
  28. Saccharomyces cerevisiae pyruvate kinase Pyk1 is PKA phosphorylation substrate in vitro. Cytryńska, M., Frajnt, M., Jakubowicz, T. FEMS Microbiol. Lett. (2001) [Pubmed]
  29. Bcy1, the regulatory subunit of cAMP-dependent protein kinase in yeast, is differentially modified in response to the physiological status of the cell. Werner-Washburne, M., Brown, D., Braun, E. J. Biol. Chem. (1991) [Pubmed]
  30. Localization of the regulatory subunit of cAMP-dependent protein kinase in Saccharomyces cerevisiae. Uno, I., Oshima, T., Ishikawa, T. Exp. Cell Res. (1988) [Pubmed]
  31. Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans. Hicks, J.K., D'Souza, C.A., Cox, G.M., Heitman, J. Eukaryotic Cell (2004) [Pubmed]
  32. AKAP7gamma is a nuclear RI-binding AKAP. Brown, R.L., August, S.L., Williams, C.J., Moss, S.B. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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