TPK2/YPL203W Summary Help

Standard Name TPK2 1
Systematic Name YPL203W
Alias PKA2 , YKR1 , PKA3
Feature Type ORF, Verified
Description cAMP-dependent protein kinase catalytic subunit; promotes vegetative growth in response to nutrients via the Ras-cAMP signaling pathway; partially redundant with Tpk1p and Tpk3p; localizes to P-bodies during stationary phase; relocalizes to the cytosol in response to hypoxia (2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description Takashi's Protein Kinase 7
Chromosomal Location
ChrXVI:166256 to 167398 | ORF Map | GBrowse
Genetic position: -120 cM
Gene Ontology Annotations All TPK2 GO evidence and references
  View Computational GO annotations for TPK2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 6 genes
Classical genetics
reduction of function
Large-scale survey
222 total interaction(s) for 146 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 49
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 7
  • Biochemical Activity: 45
  • Co-fractionation: 1
  • PCA: 1
  • Reconstituted Complex: 10
  • Two-hybrid: 9

Genetic Interactions
  • Dosage Lethality: 5
  • Dosage Rescue: 29
  • Negative Genetic: 18
  • Phenotypic Enhancement: 12
  • Phenotypic Suppression: 4
  • Positive Genetic: 6
  • Synthetic Growth Defect: 8
  • Synthetic Lethality: 7
  • Synthetic Rescue: 9

Expression Summary
Length (a.a.) 380
Molecular Weight (Da) 44,219
Isoelectric Point (pI) 7.22
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXVI:166256 to 167398 | ORF Map | GBrowse
Genetic position: -120 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1143 166256..167398 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000006124

TPK1, TPK2, and TPK3 encode isoforms of the catalytic subunit of cAMP-dependent protein kinase (PKA), the effector kinase of the Ras-cAMP signaling pathway (reviews of the Ras-cAMP pathway can be found in 8 and 9). Through phosphorylation of various targets, PKA activity regulates processes involved in cell growth and response to nutrients and stress, such as nutrient sensing, energy metabolism, carbohydrate utilzation, cell cycle progression, thermotolerance, osmotic shock tolerance, sporulation, bud site selection, pseudohyphal growth, aging, and autophagy (reviewed in 9, 10, 11, and 12). PKA substrates include transcription factors (e.g., Rap1p (13), Hsf1p (14), Adr1p (15), Msn2p / Msn4p (16, 17), Ssn2p (18)), metabolic enzymes (e.g., Cho1p (19), Pfk2p (20), Nth1p (21)), and other regulatory kinases (e.g., Rim15p (22), Atg1p (23)). The PKA target site is R-[KR]-x-S, where S is the site of substrate phosphorylation (24, 25). PKA is conserved from yeast to man and TPK homologs have been identified in fission yeast, flies, worms, mice, pigs, cows, and humans (26, and reviewed in 27).

In the absence of cAMP, the catalytic subunits (Tpk1p, 2p, or 3p) form an inactive heterotetrameric complex with the PKA regulatory subunit Bcy1p, with two catalytic subunits bound to two regulatory subunits. In the presence of cAMP, Bcy1p binds to cAMP and dissociates from the complex as a homodimer, releasing the two catalytic subunits as active monomers (2 and references therein). PKA is also regulated through a cAMP feedback inhibition loop: PKA activity leads to a reduction in cAMP levels by directly phosphorylating enzymes which regulate cAMP production, (e.g. the GTPase Ras2p and the cAMP phosphodiesterase Pde1p), and the resulting decrease in cAMP levels promotes formation of the inactive heterotetrameric complex (28, 29, 30, 31). All three Tpk isozymes are phosphorylated and the phosphorylation state of Tpk1p has been shown to affect its substrate specificity constant and to be correlated with the availability of a fermentable carbon source (32).

The three PKA catalytic subunits are highly similar only in their C-terminal regions. Although the C-terminal 320 amino acids of Tpk1p and Tpk2p share 77% identity and are 88% and 75% identical to Tpk3p respectively, the N-terminal regions of these proteins share no sequence similarity and are heterogeneous in length (2). While no single TPK gene is essential, the presence of at least one of the isomers is required for normal growth (2). Mutations affecting levels of PKA activity lead to pleiotropic phenotypes because of the wide range of PKA substrates and their involvement in many cellular processes. Phenotypes due to hyperactive PKA signaling include rapamycin resistance, accelerated pseudohyphal growth, transient cell cycle arrest in G1, and increased sensitivity to stresses such as heat shock and nutrient starvation while some of the phenotypes resulting from reduced PKA activity are hyperaccumulation of cAMP, defective glucose repression, and decreased levels of ribosomal protein mRNAs (33, 34 and references therein, and reviewed in 8).

Although the Tpk isomers are functionally redundant for cell viability, they appear to regulate different processes. One high-throughput study showed that different numbers of distinct proteins were targeted by Tpk1p (256), Tpk2p (29), and Tpk3p (79) and greater than 87% of all PKA substrates were uniquely phosphorylated by just one of the Tpks (24). In addition to protein targets, the three isomers also recognize and affect the transcription of different sets of gene targets. Tpk2p was shown to bind to the promoter region of genes encoding ribosomal proteins and in particular regulates genes involved in iron uptake, trehalose degradation, and water homeostasis (35, 36). Tpk2p also inhibits the function of the anaphase-promoting complex (APC) through possible phosphorylation of the APC activator Cdc20p (37, 38).

Last updated: 2007-05-17 Contact SGD

References cited on this page View Complete Literature Guide for TPK2
1) Petitjean, A. and Tatchell, K.  (1989) Personal Communication, Mortimer Map Edition 10
2) Toda T, et al.  (1987) Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase. Cell 50(2):277-87
3) Ordiz I, et al.  (1996) Glucose-induced inactivation of isocitrate lyase in Saccharomyces cerevisiae is mediated by the cAMP-dependent protein kinase catalytic subunits Tpk1 and Tpk2. FEBS Lett 385(1-2):43-6
4) Toda T, et al.  (1987) Cloning and characterization of BCY1, a locus encoding a regulatory subunit of the cyclic AMP-dependent protein kinase in Saccharomyces cerevisiae. Mol Cell Biol 7(4):1371-7
5) Tudisca V, et al.  (2010) Differential localization to cytoplasm, nucleus or P-bodies of yeast PKA subunits under different growth conditions. Eur J Cell Biol 89(4):339-348
6) Ghosh Dastidar R, et al.  (2012) The nuclear localization of SWI/SNF proteins is subjected to oxygen regulation. Cell Biosci 2(1):30
7) Thorner J  (2005) personal communication
8) Broach JR  (1991) RAS genes in Saccharomyces cerevisiae: signal transduction in search of a pathway. Trends Genet 7(1):28-33
9) Santangelo GM  (2006) Glucose signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 70(1):253-82
10) Estruch F  (2000) Stress-controlled transcription factors, stress-induced genes and stress tolerance in budding yeast. FEMS Microbiol Rev 24(4):469-86
11) Norbeck J and Blomberg A  (2000) The level of cAMP-dependent protein kinase A activity strongly affects osmotolerance and osmo-instigated gene expression changes in Saccharomyces cerevisiae. Yeast 16(2):121-37
12) Barbieri M, et al.  (2003) Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans. Am J Physiol Endocrinol Metab 285(5):E1064-71
13) Klein C and Struhl K  (1994) Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity. Mol Cell Biol 14(3):1920-8
14) Ferguson SB, et al.  (2005) Protein kinase A regulates constitutive expression of small heat-shock genes in an Msn2/4p-independent and Hsf1p-dependent manner in Saccharomyces cerevisiae. Genetics 169(3):1203-14
15) Cherry JR, et al.  (1989) Cyclic AMP-dependent protein kinase phosphorylates and inactivates the yeast transcriptional activator ADR1. Cell 56(3):409-19
16) Gorner W, et al.  (1998) Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Genes Dev 12(4):586-97
17) Gorner W, et al.  (2002) Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor. EMBO J 21(1-2):135-44
18) Chang YW, et al.  (2004) The Ras/PKA signaling pathway directly targets the Srb9 protein, a component of the general RNA polymerase II transcription apparatus. Mol Cell 15(1):107-16
19) Kinney AJ and Carman GM  (1988) Phosphorylation of yeast phosphatidylserine synthase in vivo and in vitro by cyclic AMP-dependent protein kinase. Proc Natl Acad Sci U S A 85(21):7962-6
20) Dihazi H, et al.  (2003) Glucose-induced stimulation of the Ras-cAMP pathway in yeast leads to multiple phosphorylations and activation of 6-phosphofructo-2-kinase. Biochemistry 42(20):6275-82
21) Zahringer H, et al.  (1998) 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. Eur J Biochem 255(3):544-51
22) Reinders A, et al.  (1998) Saccharomyces cerevisiae cAMP-dependent protein kinase controls entry into stationary phase through the Rim15p protein kinase. Genes Dev 12(18):2943-55
23) Budovskaya YV, et al.  (2005) An evolutionary proteomics approach identifies substrates of the cAMP-dependent protein kinase. Proc Natl Acad Sci U S A 102(39):13933-8
24) Ptacek J, et al.  (2005) Global analysis of protein phosphorylation in yeast. Nature 438(7068):679-84
25) Denis CL, et al.  (1991) Substrate specificities for yeast and mammalian cAMP-dependent protein kinases are similar but not identical. J Biol Chem 266(27):17932-5
26) Yu G, et al.  (1994) The Schizosaccharomyces pombe pka1 gene, encoding a homolog of cAMP-dependent protein kinase. Gene 151(1-2):215-20
27) Scott JD  (1991) Cyclic nucleotide-dependent protein kinases. Pharmacol Ther 50(1):123-45
28) Mbonyi K, et al.  (1990) Glucose-induced hyperaccumulation of cyclic AMP and defective glucose repression in yeast strains with reduced activity of cyclic AMP-dependent protein kinase. Mol Cell Biol 10(9):4518-23
29) Nikawa J, et al.  (1987) Rigorous feedback control of cAMP levels in Saccharomyces cerevisiae. Genes Dev 1(9):931-7
30) Sreenath TL, et al.  (1988) Two different protein kinase activities phosphorylate Ras2 protein in Saccharomyces cerevisiae. Biochem Biophys Res Commun 157(3):1182-9
31) Ma P, et al.  (1999) The PDE1-encoded low-affinity phosphodiesterase in the yeast Saccharomyces cerevisiae has a specific function in controlling agonist-induced cAMP signaling. Mol Biol Cell 10(1):91-104
32) Portela P and Moreno S  (2006) Glucose-dependent activation of protein kinase A activity in Saccharomyces cerevisiae and phosphorylation of its TPK1 catalytic subunit. Cell Signal 18(7):1072-86
33) Zurita-Martinez SA and Cardenas ME  (2005) Tor and cyclic AMP-protein kinase A: two parallel pathways regulating expression of genes required for cell growth. Eukaryot Cell 4(1):63-71
34) Hartley AD, et al.  (1996) cAMP inhibits bud growth in a yeast strain compromised for Ca2+ influx into the Golgi. Mol Gen Genet 251(5):556-64
35) Robertson LS, et al.  (2000) The yeast A kinases differentially regulate iron uptake and respiratory function. Proc Natl Acad Sci U S A 97(11):5984-8
36) Pokholok DK, et al.  (2006) Activated signal transduction kinases frequently occupy target genes. Science 313(5786):533-6
37) Bolte M, et al.  (2003) Synergistic inhibition of APC/C by glucose and activated Ras proteins can be mediated by each of the Tpk1-3 proteins in Saccharomyces cerevisiae. Microbiology 149(Pt 5):1205-16
38) Searle JS, et al.  (2004) The DNA damage checkpoint and PKA pathways converge on APC substrates and Cdc20 to regulate mitotic progression. Nat Cell Biol 6(2):138-45