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Gene Review

TPK1  -  cAMP-dependent protein kinase catalytic...

Saccharomyces cerevisiae S288c

Synonyms: CDC25-suppressing protein kinase, J0541, PK-25, PKA 1, PKA1, ...
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Disease relevance of TPK1


High impact information on TPK1

  • We have isolated mutant TPK genes that suppress all of the bcy1- defects [2].
  • We have isolated three genes (TPK1, TPK2, and TPK3) from the yeast S. cerevisiae that encode the catalytic subunits of the cAMP-dependent protein kinase [3].
  • The TPK1 gene carried on a multicopy plasmid can suppress both a temperature-sensitive ras2 gene and adenylate cyclase gene [3].
  • Comparison of the predicted amino acid sequences of the TPK genes indicates conserved and variable domains [3].
  • Although they are redundant for viability, the three A kinases are not redundant for pseudohyphal growth [Robertson, L. S. & Fink, G. R. (1998) Proc. Natl. Acad. Sci. USA 95, 13783-13787; Pan, X. & Heitman, J. (1999) Mol. Cell. Biol. 19, 4874-4887]; Tpk2, but not Tpk1 or Tpk3, is required for pseudohyphal growth [4].

Biological context of TPK1


Anatomical context of TPK1

  • Tpk1 is required for the derepression of branched chain amino acid biosynthesis genes that seem to have a second role in the maintenance of iron levels and DNA stability within mitochondria [4].
  • In isolated vacuoles of yeast yvc1 disruption mutants, the TPK1 gene product shows ion channel activity with some characteristics very similar to the SV-type channel [10].

Associations of TPK1 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 [11].
  • We have purified and characterized the catalytic subunit, C1, encoded by the TPK1 gene [12].
  • 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 [13].
  • SRA3 is homologous to protein kinases that phosphorylate serine and threonine and likely encodes the catalytic subunit of the cAMP-dependent protein kinase [6].
  • In order to purify C1 completely free of C2 and C3, a strain was constructed that contained only the TPK1 gene and genetic disruptions of the other two TPK genes [12].

Physical interactions of TPK1


Enzymatic interactions of TPK1

  • The strain containing TPK3 as the only intact TPK gene showed nearly undetectable phosphorylating activity and no TPK3 mRNA could be detected, although the cells grow normally [15].
  • Both glutathione S-transferase (GST)-Pyk1 and GST-Pyk2 were phosphorylated in vitro by the bovine heart protein kinase A (PKA) catalytic subunit and by immobilized yeast HA-Tpk1 [16].
  • The results indicate that either rapamycin did not suppress the derepression of sexual development of strains in which adenylate cyclase was deleted or the cyclic AMP-dependent protein kinase encoded by pka1 was mutated [17].

Regulatory relationships of TPK1


Other interactions of TPK1

  • TPK1 and TPK2 encode both isoforms of protein kinase A (PKA) catalytic subunits in Candida albicans [5].
  • TPK1, which encodes a catalytic subunit of PKA, is a multicopy suppressor of the recombination and growth defects of sch9 mutants, suggesting that increased PKA activity compensates for SCH9 loss [19].
  • 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 [20].
  • The cdc25-suppressing protein kinase (PK-25) shows 48% sequence similarity to the catalytic subunit (CA) of mammalian cAMP-dependent protein kinase and 27-31% similarity to cyclic nucleotide-independent enzymes, including the yeast CDC28 gene product [20].
  • Finally, and importantly, TOR controls the subcellular localization of both the protein kinase A catalytic subunit TPK1 and the RAS/cAMP signaling-related kinase YAK1 [21].

Analytical, diagnostic and therapeutic context of TPK1


  1. Stability of neutral trehalase during heat stress in Saccharomyces cerevisiae is dependent on the activity of the catalytic subunits of cAMP-dependent protein kinase, Tpk1 and Tpk2. Zähringer, H., Holzer, H., Nwaka, S. Eur. J. Biochem. (1998) [Pubmed]
  2. 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]
  3. Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase. Toda, T., Cameron, S., Sass, P., Zoller, M., Wigler, M. Cell (1987) [Pubmed]
  4. The yeast A kinases differentially regulate iron uptake and respiratory function. Robertson, L.S., Causton, H.C., Young, R.A., Fink, G.R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. Distinct and redundant roles of the two protein kinase A isoforms Tpk1p and Tpk2p in morphogenesis and growth of Candida albicans. Bockmühl, D.P., Krishnamurthy, S., Gerads, M., Sonneborn, A., Ernst, J.F. Mol. Microbiol. (2001) [Pubmed]
  6. Characterization of Saccharomyces cerevisiae genes encoding subunits of cyclic AMP-dependent protein kinase. Cannon, J.F., Tatchell, K. Mol. Cell. Biol. (1987) [Pubmed]
  7. Cloning of the pka1 gene encoding the catalytic subunit of the cAMP-dependent protein kinase in Schizosaccharomyces pombe. Maeda, T., Watanabe, Y., Kunitomo, H., Yamamoto, M. J. Biol. Chem. (1994) [Pubmed]
  8. Nature and transcriptional role of catalytic subunits of yeast mitochondrial cAMP-dependent protein kinase. Rahman, M.U., Hudson, A.P. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  9. The Gap1 general amino acid permease acts as an amino acid sensor for activation of protein kinase A targets in the yeast Saccharomyces cerevisiae. Donaton, M.C., Holsbeeks, I., Lagatie, O., Van Zeebroeck, G., Crauwels, M., Winderickx, J., Thevelein, J.M. Mol. Microbiol. (2003) [Pubmed]
  10. TPK1 is a vacuolar ion channel different from the slow-vacuolar cation channel. Bihler, H., Eing, C., Hebeisen, S., Roller, A., Czempinski, K., Bertl, A. Plant Physiol. (2005) [Pubmed]
  11. Cisplatin sensitivity in cAMP-dependent protein kinase mutants of Saccharomyces cerevisiae. Cvijic, M.E., Yang, W.L., Chin, K.V. Anticancer Res. (1998) [Pubmed]
  12. 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]
  13. 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]
  14. Saccharomyces cerevisiae pyruvate kinase Pyk1 is PKA phosphorylation substrate in vitro. Cytryńska, M., Frajnt, M., Jakubowicz, T. FEMS Microbiol. Lett. (2001) [Pubmed]
  15. 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]
  16. In vivo and in vitro phosphorylation of two isoforms of yeast pyruvate kinase by protein kinase A. Portela, P., Howell, S., Moreno, S., Rossi, S. J. Biol. Chem. (2002) [Pubmed]
  17. Rapamycin specifically interferes with the developmental response of fission yeast to starvation. Weisman, R., Choder, M., Koltin, Y. J. Bacteriol. (1997) [Pubmed]
  18. Direct and novel regulation of cAMP-dependent protein kinase by Mck1p, a yeast glycogen synthase kinase-3. Rayner, T.F., Gray, J.V., Thorner, J.W. J. Biol. Chem. (2002) [Pubmed]
  19. SCH9, a putative protein kinase from Saccharomyces cerevisiae, affects HOT1-stimulated recombination. Prusty, R., Keil, R.L. Mol. Genet. Genomics (2004) [Pubmed]
  20. 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]
  21. Activation of the RAS/cyclic AMP pathway suppresses a TOR deficiency in yeast. Schmelzle, T., Beck, T., Martin, D.E., Hall, M.N. Mol. Cell. Biol. (2004) [Pubmed]
  22. Crystallization and preliminary X-ray analysis of the cAMP-dependent protein kinase catalytic subunit from Saccharomyces cerevisiae. Kuret, J., Pflugrath, J.W. Biochemistry (1991) [Pubmed]
  23. 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]
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