Genomes and Genes
Gene Symbol: TPK2
Description: cAMP-dependent protein kinase catalytic subunit TPK2
Alias: PKA2, PKA3, YKR1, cAMP-dependent protein kinase catalytic subunit TPK2
Species: Saccharomyces cerevisiae S288c
- Smith A, Ward M, Garrett S. Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth, stress response and glycogen accumulation. EMBO J. 1998;17:3556-64 pubmed..These results suggest that Msn2p/Msn4p-dependent gene expression may account for all, or at least most, of the pleiotropic effects of yeast PKA, including growth regulation, response to stress and carbohydrate store accumulation. ..
- Mösch H, Kübler E, Krappmann S, Fink G, Braus G. Crosstalk between the Ras2p-controlled mitogen-activated protein kinase and cAMP pathways during invasive growth of Saccharomyces cerevisiae. Mol Biol Cell. 1999;10:1325-35 pubmed
- Searle J, Schollaert K, Wilkins B, Sanchez Y. The DNA damage checkpoint and PKA pathways converge on APC substrates and Cdc20 to regulate mitotic progression. Nat Cell Biol. 2004;6:138-45 pubmed..after DNA damage, and this phosphorylation requires the Atr orthologue Mec1 and the PKA catalytic subunits Tpk1 and Tpk2. We show that the inactivation of PKA or expression of phosphorylation-defective Cdc20 proteins accelerates securin ..
- Popova Y, Thayumanavan P, Lonati E, Agrochão M, Thevelein J. Transport and signaling through the phosphate-binding site of the yeast Pho84 phosphate transceptor. Proc Natl Acad Sci U S A. 2010;107:2890-5 pubmed publisher..Our results provide to the best of our knowledge the first insight into the molecular mechanism of a phosphate transceptor. ..
- Haesendonckx S, Tudisca V, Voordeckers K, Moreno S, Thevelein J, Portela P. The activation loop of PKA catalytic isoforms is differentially phosphorylated by Pkh protein kinases in Saccharomyces cerevisiae. Biochem J. 2012;448:307-20 pubmed publisher..Saccharomyces cerevisiae contains three PKA catalytic subunits, TPK1, TPK2 and TPK3...
- Gancedo J, Flores C, Gancedo C. The repressor Rgt1 and the cAMP-dependent protein kinases control the expression of the SUC2 gene in Saccharomyces cerevisiae. Biochim Biophys Acta. 2015;1850:1362-7 pubmed publisher..Repression is dependent on PKA activity, but not on any specific Tpk isoenzyme. The results show that previously overlooked regulatory elements, such as Rgt1 and Tpks, participate in the control of SUC2 expression in S.cerevisiae. ..
- Rutzler M, Reissaus A, Budzowska M, Bandlow W. SUT2 is a novel multicopy suppressor of low activity of the cAMP/protein kinase A pathway in yeast. Eur J Biochem. 2004;271:1284-91 pubmed
- Bolte M, Dieckhoff P, Krause C, Braus G, Irniger S. 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. 2003;149:1205-16 pubmed..Furthermore, it is shown that the three PKAs in yeast, Tpk1, Tpk2 and Tpk3, have redundant functions in regulating APC/C in response to glucose medium...
- Ansari K, Martin S, Farkasovsky M, Ehbrecht I, Küntzel H. Phospholipase C binds to the receptor-like GPR1 protein and controls pseudohyphal differentiation in Saccharomyces cerevisiae. J Biol Chem. 1999;274:30052-8 pubmed..Our data suggest that phospholipase C modulates the interaction of the putative nutrient sensor Gpr1p with the Galpha protein Gpa2p as a downstream effector of filamentation control. ..
- Stephan J, Yeh Y, Ramachandran V, Deminoff S, Herman P. The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy. Proc Natl Acad Sci U S A. 2009;106:17049-54 pubmed publisher..In all, our data indicate that the PKA and Tor pathways function independently to control autophagy in S. cerevisiae, and that the Atg1/Atg13 kinase complex is a key site of signal integration within this degradative pathway. ..
- 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. ..
- Schepers W, Van Zeebroeck G, Pinkse M, Verhaert P, Thevelein J. In vivo phosphorylation of Ser21 and Ser83 during nutrient-induced activation of the yeast protein kinase A (PKA) target trehalase. J Biol Chem. 2012;287:44130-42 pubmed publisher..Our results reveal that trehalase activation in vivo is associated with phosphorylation of typical PKA sites and thus establish the enzyme as a reliable read-out for nutrient activation of PKA in vivo...
- Makanae K, Kintaka R, Makino T, Kitano H, Moriya H. Identification of dosage-sensitive genes in Saccharomyces cerevisiae using the genetic tug-of-war method. Genome Res. 2013;23:300-11 pubmed publisher..The results obtained in this study will provide basic knowledge about the physiology of chromosomal abnormalities and the evolution of chromosomal composition. ..
- Tudisca V, Simpson C, Castelli L, Lui J, Hoyle N, Moreno S, et al. PKA isoforms coordinate mRNA fate during nutrient starvation. J Cell Sci. 2012;125:5221-32 pubmed publisher..Previously we demonstrated that PKA catalytic isoforms Tpk2 and Tpk3 localise with processing and stress bodies in Saccharomyces cerevisiae...
- Galello F, Portela P, Moreno S, Rossi S. Characterization of substrates that have a differential effect on Saccharomyces cerevisiae protein kinase A holoenzyme activation. J Biol Chem. 2010;285:29770-9 pubmed publisher..The catalytic turnover numbers of the catalytic subunits isoforms Tpk1 and Tpk2 were determined, and both enzymes are shown to have the same value of 3 s(-1)...
- Lenssen E, Oberholzer U, Labarre J, De Virgilio C, Collart M. Saccharomyces cerevisiae Ccr4-not complex contributes to the control of Msn2p-dependent transcription by the Ras/cAMP pathway. Mol Microbiol. 2002;43:1023-37 pubmed..Together, our results suggest that the Ccr4-Not complex may function as an effector of the Ras/cAMP pathway that contributes to repress basal, stress- and starvation-induced transcription by Msn2/4p. ..
- Baccarini L, MartÃnez MontaÃ±Ã©s F, Rossi S, Proft M, Portela P. PKA-chromatin association at stress responsive target genes from Saccharomyces cerevisiae. Biochim Biophys Acta. 2015;1849:1329-39 pubmed publisher..There are three PKA catalytic subunits in Saccharomyces cerevisiae: Tpk1, Tpk2, and Tpk3 and one regulatory subunit: Bcy1...
- 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. ..
- 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. ..
- Zähringer H, Holzer H, Nwaka S. 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. 1998;255:544-51 pubmed..Introduction of a plasmid carrying the TPK1 or TPK2 gene into tpk1tpk2TPK3 cells restores the heat-induced increase of neutral trehalase activity...
- Ward M, Garrett S. Suppression of a yeast cyclic AMP-dependent protein kinase defect by overexpression of SOK1, a yeast gene exhibiting sequence similarity to a developmentally regulated mouse gene. Mol Cell Biol. 1994;14:5619-27 pubmed..Overexpression of SOK1, like lesions in YAK1, also restores growth to a strain (tpk1 tpk2 tpk3) lacking all A kinase activity...
- Bharucha N, Ma J, Dobry C, Lawson S, Yang Z, Kumar A. Analysis of the yeast kinome reveals a network of regulated protein localization during filamentous growth. Mol Biol Cell. 2008;19:2708-17 pubmed publisher..Thus, the localization of Ksp1p and the other kinases identified here is tightly controlled during filamentous growth, representing an overlooked regulatory component of this stress response. ..
- Mandal A, Nillegoda N, Chen J, Caplan A. Ydj1 protects nascent protein kinases from degradation and controls the rate of their maturation. Mol Cell Biol. 2008;28:4434-44 pubmed publisher..Pulse-chase analyses revealed that a portion of Tpk2 kinase was degraded shortly after synthesis in a ydj1Delta mutant, while the remainder was capable of maturing but ..
- Pedruzzi I, Bürckert N, Egger P, De Virgilio C. Saccharomyces cerevisiae Ras/cAMP pathway controls post-diauxic shift element-dependent transcription through the zinc finger protein Gis1. EMBO J. 2000;19:2569-79 pubmed..Moreover, PDS element-driven expression, which is negatively regulated by the Ras/cAMP pathway and which is induced upon nutrient limitation, is almost entirely dependent on the presence of Gis1. ..
- 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
- Lin M, Li S, Kane P, Höfken T. Regulation of vacuolar H+-ATPase activity by the Cdc42 effector Ste20 in Saccharomyces cerevisiae. Eukaryot Cell. 2012;11:442-51 pubmed publisher..Genetic data suggest that Ste20 and the protein kinase A catalytic subunit Tpk2 are both activated in the vma13? strain...
- Kennedy E, Ghosh G, Pillus L. Identification of functionally distinct regions that mediate biological activity of the protein kinase a homolog Tpk2. J Biol Chem. 2008;283:1084-93 pubmed..kinases can be critical, we took an unbiased genetic approach to identify sites within the protein kinase A homolog Tpk2 that contribute to its biological activity...
- Duan R, Rhie B, Ryu H, Ahn S. The RNA polymerase II Rpb4/7 subcomplex regulates cellular lifespan through an mRNA decay process. Biochem Biophys Res Commun. 2013;441:266-70 pubmed..Tandem affinity purification experiments demonstrated that Rpb7 physically associates with Tpk2 and Pat1, which are both implicated in mRNA degradation...
- Bermejo C, Haerizadeh F, Sadoine M, Chermak D, Frommer W. Differential regulation of glucose transport activity in yeast by specific cAMP signatures. Biochem J. 2013;452:489-97 pubmed publisher..During starvation, cAMP levels remain low triggering expression of HXT5, whereas cAMP spiking leads to a shift to the high capacity Hxt isoforms. ..
- Roy J, Mitra S, Sengupta K, Mandal A. Hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments. Mol Biol Cell. 2015;26:1583-600 pubmed publisher..Thus active participation of SSA1 in the degradation of misfolded proteins establishes an essential role of Hsp70 in deciding client fate during stress. ..
- Choi H, Han G, Carman G. Phosphorylation of yeast phosphatidylserine synthase by protein kinase A: identification of Ser46 and Ser47 as major sites of phosphorylation. J Biol Chem. 2010;285:11526-36 pubmed publisher..These results indicate that phosphatidylserine synthase is phosphorylated on Ser(46) and Ser(47) by protein kinase A, which results in a higher amount of enzyme for the net effect of stimulating the synthesis of phosphatidylserine. ..
- Mandal A, Lee P, Chen J, Nillegoda N, Heller A, DiStasio S, et al. Cdc37 has distinct roles in protein kinase quality control that protect nascent chains from degradation and promote posttranslational maturation. J Cell Biol. 2007;176:319-28 pubmed..Our studies demonstrate that Cdc37 has a general role in kinome biogenesis. ..
- 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..in vitro reveal that it is not essential for growth and that its loss confers growth to a strain deleted for tpk1, tpk2, and tpk3, the structural genes for the catalytic subunit of the cAMP-dependent protein kinase...
- Dong J, Bai X. The membrane localization of Ras2p and the association between Cdc25p and Ras2-GTP are regulated by protein kinase A (PKA) in the yeast Saccharomyces cerevisiae. FEBS Lett. 2011;585:1127-34 pubmed publisher..These results suggest that Ras2p localization and Ras2-GEF activity of Cdc25p play roles in the feedback regulation of Ras2p in the Ras-cAMP pathway. ..
- Mizunuma M, Tsubakiyama R, Ogawa T, Shitamukai A, Kobayashi Y, Inai T, et al. Ras/cAMP-dependent protein kinase (PKA) regulates multiple aspects of cellular events by phosphorylating the Whi3 cell cycle regulator in budding yeast. J Biol Chem. 2013;288:10558-66 pubmed publisher..Thus, PKA modulated the function of Whi3 by phosphorylation, thus implicating PKA-mediated modulation of Whi3 in multiple cellular events. ..
- van Dyk D, Pretorius I, Bauer F. Mss11p is a central element of the regulatory network that controls FLO11 expression and invasive growth in Saccharomyces cerevisiae. Genetics. 2005;169:91-106 pubmed..Taken together, the data strongly suggest a central role for Mss11p in the regulatory network controlling FLO11 expression, invasive growth, and pseudohyphal differentiation. ..
- Searle J, Wood M, Kaur M, Tobin D, Sanchez Y. Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage. PLoS Genet. 2011;7:e1002176 pubmed publisher..Our data indicate that there is cross-talk between the DNA damage checkpoint and the proteins that integrate nutrient and stress signals to regulate PKA. ..
- Zurita Martinez S, Cardenas M. Tor and cyclic AMP-protein kinase A: two parallel pathways regulating expression of genes required for cell growth. Eukaryot Cell. 2005;4:63-71 pubmed
- Ren M, Santhanam A, Lee P, Caplan A, Garrett S. Alteration of the protein kinase binding domain enhances function of the Saccharomyces cerevisiae molecular chaperone Cdc37. Eukaryot Cell. 2007;6:1363-72 pubmed..of Cdc37 that alleviate the conditional growth defect of a strain containing a temperature-sensitive allele, tpk2(Ts), of the cyclic AMP-dependent protein kinase (PKA)...
- Park Y, Hwang O, Kim J. Two-hybrid cloning and characterization of OSH3, a yeast oxysterol-binding protein homolog. Biochem Biophys Res Commun. 2002;293:733-40 pubmed..These results lead us to a new understanding of cellular functions of the yeast OSBPs. ..
- 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
- Nehlin J, Carlberg M, Ronne H. Yeast SKO1 gene encodes a bZIP protein that binds to the CRE motif and acts as a repressor of transcription. Nucleic Acids Res. 1992;20:5271-8 pubmed..Third, in the absence of MIG1, there is also a rapid but transient glucose induction of the SUC2 mRNA. This induction is correlated with a transient loss of SKO1-dependent repression. ..
- Legesse Miller A, Zhang S, Santiago Tirado F, Van Pelt C, Bretscher A. Regulated phosphorylation of budding yeast's essential myosin V heavy chain, Myo2p. Mol Biol Cell. 2006;17:1812-21 pubmed..These results suggest that in yeast, Myo2p is subject to phosphoregulation involving a PKA-related signaling pathway. ..
- Duan R, Rhie B, Ryu H, Ahn S. The RNA polymerase II Rpb4/7 subcomplex regulates cellular lifespan through an mRNA decay process. Biochem Biophys Res Commun. 2013;: pubmed publisher..Tandem affinity purification experiments demonstrated that Rpb7 physically associates with Tpk2 and Pat1, which are both implicated in mRNA degradation...
- Harashima T, Heitman J. The Galpha protein Gpa2 controls yeast differentiation by interacting with kelch repeat proteins that mimic Gbeta subunits. Mol Cell. 2002;10:163-73 pubmed..Our studies demonstrate that Gpa2 signals in conjunction with Gbeta structural mimics and that homologous G protein subunits or effectors may be conserved in multicellular eukaryotes. ..
- Bavli Kertselli I, Melamed D, Bar Ziv L, Volf H, Arava Y. Overexpression of eukaryotic initiation factor 5 rescues the translational defect of tpk1w in a manner that necessitates a novel phosphorylation site. FEBS J. 2015;282:504-20 pubmed publisher..These results implicate phosphorylation of eIF5 at Thr191 by CKII as one of the pathways for regulating translation upon glucose depletion. ..
- PÃ©rez Landero S, Sandoval Motta S, MartÃnez Anaya C, Yang R, Folch Mallol J, MartÃnez L, et al. Complex regulation of Hsf1-Skn7 activities by the catalytic subunits of PKA in Saccharomyces cerevisiae: experimental and computational evidences. BMC Syst Biol. 2015;9:42 pubmed publisher..Further modeling of the new data foresaw a third repressor of Hsf1/Skn7, active only in the absence of Tpk2. By averaging the network state over all its attractors, a good quantitative agreement between computational and ..
- 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. ..
- Kim J, Johnston M. Two glucose-sensing pathways converge on Rgt1 to regulate expression of glucose transporter genes in Saccharomyces cerevisiae. J Biol Chem. 2006;281:26144-9 pubmed..Thus, two different glucose signal transduction pathways converge on Rgt1 to regulate expression of glucose transporters. ..
- Reinders A, Bürckert N, Boller T, Wiemken A, De Virgilio C. Saccharomyces cerevisiae cAMP-dependent protein kinase controls entry into stationary phase through the Rim15p protein kinase. Genes Dev. 1998;12:2943-55 pubmed..Taken together, these results place Rim15p immediately downstream and under negative control of cAPK and define a positive regulatory role of Rim15p for entry into both meiosis and stationary phase. ..
- Torbensen R, Møller H, Gresham D, Alizadeh S, Ochmann D, Boles E, et al. Amino acid transporter genes are essential for FLO11-dependent and FLO11-independent biofilm formation and invasive growth in Saccharomyces cerevisiae. PLoS ONE. 2012;7:e41272 pubmed publisher..Increased intracellular amino acid pools in the PTR3(647::CWNKNPLSSIN)-containing strain opens the possibility that Gap1 regulates the FLO genes through alteration of the amino acid pool sizes. ..
- Malcher M, Schladebeck S, Mösch H. The Yak1 protein kinase lies at the center of a regulatory cascade affecting adhesive growth and stress resistance in Saccharomyces cerevisiae. Genetics. 2011;187:717-30 pubmed publisher..In summary, our data suggest that Yak1 is at the center of a regulatory cascade for adhesive growth and stress resistance, which is under dual control of Whi3 and the PKA subunit Tpk1. ..