Gene Symbol: PBS2
Description: mitogen-activated protein kinase kinase PBS2
Alias: HOG4, SFS4, SSK4, mitogen-activated protein kinase kinase PBS2
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Posas F, Saito H. Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator. EMBO J. 1998;17:1385-94 pubmed
    ..the HOG1 mitogen-activated protein kinase (MAPK) cascade, which is composed of SSK2, SSK22 and STE11 MAPKKKs, PBS2 MAPKK and HOG1 MAPK...
  2. Wurgler Murphy S, Maeda T, Witten E, Saito H. Regulation of the Saccharomyces cerevisiae HOG1 mitogen-activated protein kinase by the PTP2 and PTP3 protein tyrosine phosphatases. Mol Cell Biol. 1997;17:1289-97 pubmed
    ..However, expression of constitutively active mutant kinases, such as those encoded by SSK2deltaN and PBS2(DD), is toxic and results in a lethal level of Hog1p activation...
  3. Posas F, Saito H. Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK. Science. 1997;276:1702-5 pubmed
    ..The MAPKK Pbs2p bound to the Sho1p osmosensor, the MAPKKK Ste11p, and the MAPK Hog1p. Thus, Pbs2p may serve as a scaffold protein. ..
  4. Maeda T, Takekawa M, Saito H. Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor. Science. 1995;269:554-8 pubmed
    ..Mutants that were not able to activate PBS2 MAP kinase kinase (MAPKK; Pbs2p) at high osmolarity were characterized...
  5. Zarrinpar A, Bhattacharyya R, Nittler M, Lim W. Sho1 and Pbs2 act as coscaffolds linking components in the yeast high osmolarity MAP kinase pathway. Mol Cell. 2004;14:825-32 pubmed
    ..In the yeast high osmolarity response pathway, the MAP kinase kinase Pbs2 is thought to function as a scaffold, since it binds the osmosensor Sho1, the upstream MAP kinase kinase kinase ..
  6. Mapes J, Ota I. Nbp2 targets the Ptc1-type 2C Ser/Thr phosphatase to the HOG MAPK pathway. EMBO J. 2004;23:302-11 pubmed
    The yeast high osmolarity glycerol (HOG) pathway signals via the Pbs2 MEK and the Hog1 MAPK, whose activity requires phosphorylation of Thr and Tyr in the activation loop...
  7. Murakami Y, Tatebayashi K, Saito H. Two adjacent docking sites in the yeast Hog1 mitogen-activated protein (MAP) kinase differentially interact with the Pbs2 MAP kinase kinase and the Ptp2 protein tyrosine phosphatase. Mol Cell Biol. 2008;28:2481-94 pubmed publisher
    ..mechanism by which the yeast osmoregulatory Hog1 MAPK specifically interacts with its activator, the MAPK kinase Pbs2, and its major inactivator, the protein phosphatase Ptp2...
  8. Alepuz P, de Nadal E, Zapater M, Ammerer G, Posas F. Osmostress-induced transcription by Hot1 depends on a Hog1-mediated recruitment of the RNA Pol II. EMBO J. 2003;22:2433-42 pubmed
    ..The mammalian p38 also interacts with the RNA Pol II, which might suggest a conserved mechanism for regulation of gene expression by SAPKs among eukaryotic cells. ..
  9. Brewster J, de Valoir T, Dwyer N, Winter E, Gustin M. An osmosensing signal transduction pathway in yeast. Science. 1993;259:1760-3 pubmed
    ..Two of these genes, HOG1 and PBS2, encode members of the mitogen-activated protein kinase (MAP kinase) and MAP kinase kinase gene families, ..

More Information


  1. Posas F, Wurgler Murphy S, Maeda T, Witten E, Thai T, Saito H. Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 "two-component" osmosensor. Cell. 1996;86:865-75 pubmed
    ..We propose that the multistep phosphorelay mechanism is a universal signal transduction apparatus utilized both in prokaryotes and eukaryotes. ..
  2. Davenport K, Williams K, Ullmann B, Gustin M. Activation of the Saccharomyces cerevisiae filamentation/invasion pathway by osmotic stress in high-osmolarity glycogen pathway mutants. Genetics. 1999;153:1091-103 pubmed
    ..We utilized a partial loss-of-function mutant in the HOG pathway, pbs2-3, in a high-copy suppressor screen to identify proteins that modulate growth on high-osmolarity media...
  3. Brewster J, Gustin M. Positioning of cell growth and division after osmotic stress requires a MAP kinase pathway. Yeast. 1994;10:425-39 pubmed
    ..Mutants lacking the mitogen-activated protein (MAP) kinase encoded by HOG1 or the MAP kinase kinase encoded by PBS2 (previously HOG4) show a similar growth arrest after osmotic stress...
  4. Bilsland Marchesan E, Arino J, Saito H, Sunnerhagen P, Posas F. Rck2 kinase is a substrate for the osmotic stress-activated mitogen-activated protein kinase Hog1. Mol Cell Biol. 2000;20:3887-95 pubmed
    ..Taken together, our data suggest that Rck2 acts downstream of Hog1, controlling a subset of the responses induced by the MAPK upon osmotic stress. ..
  5. O Rourke S, Herskowitz I. The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae. Genes Dev. 1998;12:2874-86 pubmed
    ..We found that mutations in the HOG1 gene, encoding the p38-type MAPK of the HOG pathway, and in the PBS2 gene, encoding the activating kinase for Hog1p, allowed osmolarity-induced activation of the pheromone response ..
  6. Marles J, Dahesh S, Haynes J, Andrews B, Davidson A. Protein-protein interaction affinity plays a crucial role in controlling the Sho1p-mediated signal transduction pathway in yeast. Mol Cell. 2004;14:813-23 pubmed
    ..Our experiments also indicate that a second binding surface on the Sho1p SH3 domain is required for its proper in vivo function. ..
  7. García Rodriguez L, Duran A, Roncero C. Calcofluor antifungal action depends on chitin and a functional high-osmolarity glycerol response (HOG) pathway: evidence for a physiological role of the Saccharomyces cerevisiae HOG pathway under noninducing conditions. J Bacteriol. 2000;182:2428-37 pubmed
    We have isolated several Saccharomyces cerevisiae mutants resistant to calcofluor that contain mutations in the PBS2 or HOG1 genes, which encode the mitogen-activated protein kinase (MAPK) and MAP kinases, respectively, of the high-..
  8. Kahn R, Clark J, Rulka C, Stearns T, Zhang C, Randazzo P, et al. Mutational analysis of Saccharomyces cerevisiae ARF1. J Biol Chem. 1995;270:143-50 pubmed
    ..Two high-copy suppressors of this conditional phenotype were cloned and sequenced. One of these suppressors, SFS4, was found to be identical to PBS2/HOG4, recently shown to encode a microtubule-associated protein kinase kinase in yeast.
  9. Winkler A, Arkind C, Mattison C, Burkholder A, Knoche K, Ota I. Heat stress activates the yeast high-osmolarity glycerol mitogen-activated protein kinase pathway, and protein tyrosine phosphatases are essential under heat stress. Eukaryot Cell. 2002;1:163-73 pubmed
    ..Second, they block inappropriate cross talk between the HOG and the cell wall integrity MAPK pathways, suggesting that PTPs are important for maintaining specificity in MAPK signaling pathways. ..
  10. Tsujimoto Y, Izawa S, Inoue Y. Cooperative regulation of DOG2, encoding 2-deoxyglucose-6-phosphate phosphatase, by Snf1 kinase and the high-osmolarity glycerol-mitogen-activated protein kinase cascade in stress responses of Saccharomyces cerevisiae. J Bacteriol. 2000;182:5121-6 pubmed
    ..These results suggest that Snf1p kinase and the high-osmolarity glycerol-mitogen-activated protein kinase cascade are likely to be involved in the signaling pathway of oxidative stress and osmotic stress in regulation of DOG2. ..
  11. Zuzuarregui A, Li T, Friedmann C, Ammerer G, Alepuz P. Msb2 is a Ste11 membrane concentrator required for full activation of the HOG pathway. Biochim Biophys Acta. 2015;1849:722-30 pubmed publisher
    ..Msb2 or Hkr1 is necessary for observing the interaction between Ste11 and scaffolding factors such as Sho1 and Pbs2. Additional assays suggest that Msb2 is not only in close proximity to Ste11 but might function as an individual ..
  12. Boysen J, Fanning S, Newberg J, Murphy R, Mitchell A. Detection of protein-protein interactions through vesicle targeting. Genetics. 2009;182:33-9 pubmed publisher
    ..cerevisiae and the fungal pathogen Candida albicans. We use computational analysis of microscopic images to provide a quantitative and automated assessment of confidence. ..
  13. Labedzka K, Tian C, Nussbaumer U, Timmermann S, Walther P, Müller J, et al. Sho1p connects the plasma membrane with proteins of the cytokinesis network through multiple isomeric interaction states. J Cell Sci. 2012;125:4103-13 pubmed publisher
    ..Owing to the overlapping binding specificities of its members the HICS complex is best described as ensembles of isomeric interaction states that precisely coordinate the different functions of the interactors during cytokinesis. ..
  14. Li S, Diakov T, Rizzo J, Kane P. Vacuolar H+-ATPase works in parallel with the HOG pathway to adapt Saccharomyces cerevisiae cells to osmotic stress. Eukaryot Cell. 2012;11:282-91 pubmed publisher
    ..vma2? hog1? and vma3? pbs2? double mutants have a synthetic growth phenotype, poor salt tolerance, and an aberrant, hyper-elongated morphology ..
  15. Furukawa K, Sidoux Walter F, Hohmann S. Expression of the yeast aquaporin Aqy2 affects cell surface properties under the control of osmoregulatory and morphogenic signalling pathways. Mol Microbiol. 2009;74:1272-86 pubmed publisher
    ..Our observations suggest a potential link between aquaporins and cell surface properties, and relate to the proposed role of mammalian aquaporins in tumour cell migration and invasion. ..
  16. Klein M, Morillas M, Vendrell A, Brive L, Gebbia M, Wallace I, et al. Design, synthesis and characterization of a highly effective inhibitor for analog-sensitive (as) kinases. PLoS ONE. 2011;6:e20789 pubmed publisher
    ..The results from this screen emphasize the need for caution and for case-by-case assessment when using the Analog-Sensitive Kinase Allele technology to assess the physiological roles of kinases. ..
  17. Boguslawski G. PBS2, a yeast gene encoding a putative protein kinase, interacts with the RAS2 pathway and affects osmotic sensitivity of Saccharomyces cerevisiae. J Gen Microbiol. 1992;138:2425-32 pubmed
    The yeast gene PBS2 encodes a presumed protein kinase. The gene is essential for manifestation of resistance to the antibiotic polymyxin B...
  18. Krantz M, Ahmadpour D, Ottosson L, Warringer J, Waltermann C, Nordlander B, et al. Robustness and fragility in the yeast high osmolarity glycerol (HOG) signal-transduction pathway. Mol Syst Biol. 2009;5:281 pubmed publisher
    ..Thus, in vivo robustness data can be used to discriminate and improve mathematical models. ..
  19. Rempola B, Kaniak A, Migdalski A, Rytka J, Slonimski P, di Rago J. Functional analysis of RRD1 (YIL153w) and RRD2 (YPL152w), which encode two putative activators of the phosphotyrosyl phosphatase activity of PP2A in Saccharomyces cerevisiae. Mol Gen Genet. 2000;262:1081-92 pubmed
    ..The rrd1,2delta mutant was partially rescued by inactivation of HOG1 or PBS2, suggesting an interaction between the RRD genes and the Hog1p signal transduction pathway...
  20. Ferrigno P, Posas F, Koepp D, Saito H, Silver P. Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1. EMBO J. 1998;17:5606-14 pubmed
    ..kinase cascade, which is composed of three tiers of protein kinases, namely the SSK2, SSK22 and STE11 MAPKKKs, the PBS2 MAPKK, and the HOG1 MAPK...
  21. Cullen P, Schultz J, Horecka J, Stevenson B, Jigami Y, Sprague G. Defects in protein glycosylation cause SHO1-dependent activation of a STE12 signaling pathway in yeast. Genetics. 2000;155:1005-18 pubmed
  22. Stevenson B, Ferguson B, De Virgilio C, Bi E, Pringle J, Ammerer G, et al. Mutation of RGA1, which encodes a putative GTPase-activating protein for the polarity-establishment protein Cdc42p, activates the pheromone-response pathway in the yeast Saccharomyces cerevisiae. Genes Dev. 1995;9:2949-63 pubmed
    ..The second mutation present in the original mutant proved to be an allele of a known gene, PBS2, which encodes a putative protein kinase that functions in the high osmolarity stress pathway...
  23. Reiser V, Salah S, Ammerer G. Polarized localization of yeast Pbs2 depends on osmostress, the membrane protein Sho1 and Cdc42. Nat Cell Biol. 2000;2:620-7 pubmed
    ..high external osmolarity leads to the activation of a p38-related mitogen-activated protein (MAP) kinase though Pbs2. Pbs2 tagged with green fluorescent protein (Pbs2-GFP) is evenly distributed in the cytoplasm but excluded from the ..
  24. Tatebayashi K, Takekawa M, Saito H. A docking site determining specificity of Pbs2 MAPKK for Ssk2/Ssk22 MAPKKKs in the yeast HOG pathway. EMBO J. 2003;22:3624-34 pubmed
    ..MAPK pathway, which consists of two upstream branches (SHO1 and SLN1) and common downstream elements including the Pbs2 MAPKK and the Hog1 MAPK...
  25. Akhtar N, Pahlman A, Larsson K, Corbett A, Adler L. SGD1 encodes an essential nuclear protein of Saccharomyces cerevisiae that affects expression of the GPD1 gene for glycerol 3-phosphate dehydrogenase. FEBS Lett. 2000;483:87-92 pubmed
    ..results in loss of cell viability, while an increased dosage of SGD1 partially suppresses the osmosensitivity of pbs2 delta and hog1 delta mutants that are defective in the osmosignaling high osmolarity glycerol (HOG) mitogen-..
  26. Sharma P, Mondal A. Evidence that C-terminal non-kinase domain of Pbs2p has a role in high osmolarity-induced nuclear localization of Hog1p. Biochem Biophys Res Commun. 2005;328:906-13 pubmed
    ..Previously we have isolated a PBS2 homologue (DPBS2) from osmo-tolerant and salt-tolerant yeast Debaryomyces hansenii that partially complemented pbs2 ..
  27. Birkaya B, Maddi A, Joshi J, Free S, Cullen P. Role of the cell wall integrity and filamentous growth mitogen-activated protein kinase pathways in cell wall remodeling during filamentous growth. Eukaryot Cell. 2009;8:1118-33 pubmed publisher
    ..Disruption of ss-1,3-glucan linkages induced mucin shedding and resulted in defects in cell-cell adhesion and invasion of cells into the agar matrix. ..
  28. Yu D, Zhang X, Liu X, Bao X, Gao D. [Identification of the gene correlated with salt stress in the Saccharomyces cerevisiae 263-H9 mutant]. Yi Chuan. 2006;28:1294-8 pubmed
    ..On the other hand, the hypersensitivity to salt and other stress conditions was due to the deletion of 5 base pairs close to position 936 bp in the PBS2 gene essential for HOG signal pathway regulation under salt stress.
  29. Bettinger B, Clark M, Amberg D. Requirement for the polarisome and formin function in Ssk2p-mediated actin recovery from osmotic stress in Saccharomyces cerevisiae. Genetics. 2007;175:1637-48 pubmed
    ..These results suggest that Ssk2p acts downstream of Bud6p and Pea2p and upstream of tropomyosin to drive actin recovery, possibly by upregulating the actin nucleation activity of the formins. ..
  30. Alonso Monge R, Real E, Wojda I, Bebelman J, Mager W, Siderius M. Hyperosmotic stress response and regulation of cell wall integrity in Saccharomyces cerevisiae share common functional aspects. Mol Microbiol. 2001;41:717-30 pubmed
    ..Here, we show that the same holds true for the other commonly used HOG pathway mutant strains pbs2 and sho1ssk2ssk22, but not for ste11ssk2ssk22...
  31. Vendrell A, Martínez Pastor M, Gonzalez Novo A, Pascual Ahuir A, Sinclair D, Proft M, et al. Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress-activated protein kinase. EMBO Rep. 2011;12:1062-8 pubmed publisher
    ..Sir2 is involved in protection against Hog1-induced cell death and can suppress Hog1-induced ROS accumulation. Therefore, cell death seems to be dictated by the balance of ROS induced by Hog1 and the protective effect of Sir2. ..
  32. Jiang L, Niu S, Clines K, Burke D, Sturgill T. Analyses of the effects of Rck2p mutants on Pbs2pDD-induced toxicity in Saccharomyces cerevisiae identify a MAP kinase docking motif, and unexpected functional inactivation due to acidic substitution of T379. Mol Genet Genomics. 2004;271:208-19 pubmed
    ..Rck2 T379E was sufficiently inactive in an rck2Delta strain to allow some cells to survive PBS2DD toxicity even when overexpressed. The significance of these findings for our understanding of Rck2p function is discussed. ..
  33. Won A, Garbarino J, Lim W. Recruitment interactions can override catalytic interactions in determining the functional identity of a protein kinase. Proc Natl Acad Sci U S A. 2011;108:9809-14 pubmed publisher
    ..We find that two alternative MAPKKs, Pbs2 and Mkk2, can be forced to functionally replace the mating MAPKK Ste7, but only if the proper set of recruitment ..
  34. 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. ..
  35. Zhou J, Zhong Q, Li G, Greenberg M. Loss of cardiolipin leads to longevity defects that are alleviated by alterations in stress response signaling. J Biol Chem. 2009;284:18106-14 pubmed publisher
    ..These findings show for the first time that perturbation of CL synthesis leads to decreased longevity in yeast, which is restored by altering signaling through stress response pathways. ..
  36. Kejžar A, Cibic M, Grøtli M, Plemenitaš A, Lenassi M. The unique characteristics of HOG pathway MAPKs in the extremely halotolerant Hortaea werneckii. FEMS Microbiol Lett. 2015;362:fnv046 pubmed publisher
    ..cerevisiae homologues. The reported findings contribute to defining the key determinants of H. werneckii osmotolerance, which is important for its potential transfer to economically relevant microorganisms and crops. ..
  37. Tesker M, Selamat S, Beenstock J, Hayouka R, Livnah O, Engelberg D. Tighter ?C-helix-?L16-helix interactions seem to make p38? less prone to activation by autophosphorylation than Hog1. Biosci Rep. 2016;36: pubmed publisher
    ..The suppressors were kept wobbly, probably to allow activation by induced autophosphorylation, but became stricter in mammalian p38s than in the yeast Hog1. ..
  38. Nishimura A, Yamamoto K, Oyama M, Kozuka Hata H, Saito H, Tatebayashi K. Scaffold Protein Ahk1, Which Associates with Hkr1, Sho1, Ste11, and Pbs2, Inhibits Cross Talk Signaling from the Hkr1 Osmosensor to the Kss1 Mitogen-Activated Protein Kinase. Mol Cell Biol. 2016;36:1109-23 pubmed publisher
    ..Hkr1-cyto binding, Ahk1 also bound to other signaling molecules in the HKR1 subbranch, including Sho1, Ste11, and Pbs2. Although osmotic stimulation of Hkr1 does not activate the Kss1 MAPK, deletion of AHK1 allowed Hkr1 to activate ..
  39. Toh e A, Oguchi T. Defects in glycosylphosphatidylinositol (GPI) anchor synthesis activate Hog1 kinase and confer copper-resistance in Saccharomyces cerevisisae. Genes Genet Syst. 2001;76:393-410 pubmed
    ..One of the Cus genes was found to be PBS2, which encodes Hog1 MAP kinase kinase, indicating that the Hog1 MAP kinase pathway is needed for the expression of ..
  40. Zuzuarregui A, Kupka T, Bhatt B, Dohnal I, Mudrak I, Friedmann C, et al. M-Track: detecting short-lived protein-protein interactions in vivo. Nat Methods. 2012;9:594-6 pubmed publisher
  41. Gorelik M, Stanger K, Davidson A. A Conserved residue in the yeast Bem1p SH3 domain maintains the high level of binding specificity required for function. J Biol Chem. 2011;286:19470-7 pubmed publisher
  42. Wang X, Sheff M, Simpson D, Elion E. Ste11p MEKK signals through HOG, mating, calcineurin and PKC pathways to regulate the FKS2 gene. BMC Mol Biol. 2011;12:51 pubmed publisher
    ..The patterns of control by Ste11p targets revealed novel functional linkages, cross-regulation, redundancy and compensation. ..
  43. Rosonina E, Willis I, Manley J. Sub1 functions in osmoregulation and in transcription by both RNA polymerases II and III. Mol Cell Biol. 2009;29:2308-21 pubmed publisher
  44. Bilsland E, Molin C, Swaminathan S, Ramne A, Sunnerhagen P. Rck1 and Rck2 MAPKAP kinases and the HOG pathway are required for oxidative stress resistance. Mol Microbiol. 2004;53:1743-56 pubmed
    ..We show that Hog1 is robustly phosphorylated in a Pbs2-dependent way during oxidative stress, and that Rck2 also is phosphorylated under these circumstances...
  45. Zarrinpar A, Park S, Lim W. Optimization of specificity in a cellular protein interaction network by negative selection. Nature. 2003;426:676-80 pubmed
    ..Here we show that an isolated peptide ligand from the yeast protein Pbs2 recognizes its biological partner, the SH3 domain from Sho1, with near-absolute specificity--no other SH3 domain ..
  46. Adhikari H, Cullen P. Metabolic respiration induces AMPK- and Ire1p-dependent activation of the p38-Type HOG MAPK pathway. PLoS Genet. 2014;10:e1004734 pubmed publisher
    ..Thus, an evolutionarily conserved regulatory axis links metabolic respiration and AMPK to Ire1p, which regulates a differentiation response involving the modulated activity of ERK and p38 MAPK pathways. ..
  47. Yamamoto K, Tatebayashi K, Tanaka K, Saito H. Dynamic control of yeast MAP kinase network by induced association and dissociation between the Ste50 scaffold and the Opy2 membrane anchor. Mol Cell. 2010;40:87-98 pubmed publisher
    ..Thus, dynamic regulation of Ste50-Opy2 interaction fine-tunes the MAPK signaling network. ..