PBS2/YJL128C Summary Help

Standard Name PBS2 1
Systematic Name YJL128C
Alias HOG4 , SFS4 , SSK4 2 , 3
Feature Type ORF, Verified
Description MAP kinase kinase of the HOG signaling pathway; activated under severe osmotic stress; mitophagy-specific regulator; plays a role in regulating Ty1 transposition (4, 5, 6 and see Summary Paragraph)
Name Description Polymyxin B Sensitivity 1
Chromosomal Location
ChrX:180103 to 178097 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -85 cM
Gene Ontology Annotations All PBS2 GO evidence and references
  View Computational GO annotations for PBS2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 4 genes
Classical genetics
Large-scale survey
584 total interaction(s) for 288 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 25
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 10
  • Biochemical Activity: 11
  • PCA: 7
  • Protein-peptide: 2
  • Reconstituted Complex: 8
  • Two-hybrid: 8

Genetic Interactions
  • Dosage Growth Defect: 2
  • Dosage Lethality: 1
  • Dosage Rescue: 17
  • Negative Genetic: 393
  • Phenotypic Enhancement: 7
  • Phenotypic Suppression: 5
  • Positive Genetic: 50
  • Synthetic Growth Defect: 9
  • Synthetic Haploinsufficiency: 2
  • Synthetic Lethality: 3
  • Synthetic Rescue: 21

Expression Summary
Length (a.a.) 668
Molecular Weight (Da) 72,720
Isoelectric Point (pI) 9.44
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrX:180103 to 178097 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -85 cM
Last Update Coordinates: 2011-02-03 | Sequence: 2011-02-03
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2007 180103..178097 2011-02-03 2011-02-03
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 SGDIDS000003664

PBS2 encodes a mitogen-activated protein kinase kinase (MAPKK) and scaffold protein integral to the osmoregulatory signal transduction cascade (HOG signaling pathway) which affects gene expression, G1 and G2 cell cycle progression, and cellular ion levels in response to hyperosmotic stress (7, 8 and a comprehensive review of the HOG pathway can be found in 9). PBS2 is conserved from yeast to man; homologs have been identified other organisms that include other fungi, plants, worms, frogs, and humans (10, 11, 12, 13, 14, 15).

Shortly after exposure to hyperosmotic stress, Pbs2p is phosphorylated by one of three MAPKKKs (Ssk2p, Ssk22p, or Ste11p), and activated Pbs2p in turn phosphorylates the MAPK Hog1p (16, 8, 7). Ssk2p and Ssk22p phosphorylation occurs under severe osmotic stress, and specificity of this interaction is mediated by a Ssk2p/Ssk22p docking site in Pbs2p (17). Ste11p activation of Pbs2p occurs under less severe hyperosmotic conditions and is triggered by the osmosensor Sho1p. Under these conditions, the non-catalytic domain of Pbs2p interacts directly with an SH3 domain in Sho1p (16), and Pbs2p acts as a scaffold that brings together Sho1p, the Ste11p MAPKKK, and the Hog1p MAPK (8 and reviewed in 9 and 18).

Pbs2p contains both a C-terminal nuclear localization signal and an N-terminal nuclear export signal, and is observed to be cytoplasmically localized. The function of the signal sequences is unclear, since deletion of either or both domains does not affect HOG pathway activation (17 and reviewed in 19). In budding cells, exposure to osmostress has been shown to affect the sub-cytoplasmic localization of a catalytically inactive form of Pbs2p, inducing a transient, Sho1p- and Cdc24p-dependent localization to the growing bud tip or to the bud neck (20).

Deletion strains of pbs2 are hypersensitive to laminarinase and K1 killer toxin, and cease to grow when exposed to exogenous pheromone or high-osmolarity (reviewed in 21). In addition to growth arrest, osmostress of pbs2 null cells also results in abnormal morphology and eventual death (22). Overexpression of PBS2 can confer increased resistance to killer toxin, but does decrease cellular response to mating pheromone and cause growth arrest (22, 23, 24).

Last updated: 2007-01-25 Contact SGD

References cited on this page View Complete Literature Guide for PBS2
1) Boguslawski G and Polazzi JO  (1987) Complete nucleotide sequence of a gene conferring polymyxin B resistance on yeast: similarity of the predicted polypeptide to protein kinases. Proc Natl Acad Sci U S A 84(16):5848-52
2) Maeda T, et al.  (1994) A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature 369(6477):242-5
3) Mao K, et al.  (2011) Two MAPK-signaling pathways are required for mitophagy in Saccharomyces cerevisiae. J Cell Biol 193(4):755-67
4) Van Wuytswinkel O, et al.  (2000) Response of Saccharomyces cerevisiae to severe osmotic stress: evidence for a novel activation mechanism of the HOG MAP kinase pathway. Mol Microbiol 37(2):382-97
5) Bansal PK, et al.  (2001) A PBS2 homologue from Debaryomyces hansenii shows a differential effect on calcofluor and polymyxin B sensitivity in Saccharomyces cerevisiae. Yeast 18(13):1207-16
6) Nyswaner KM, et al.  (2008) Chromatin-associated genes protect the yeast genome from ty1 insertional mutagenesis. Genetics 178(1):197-214
7) Brewster JL, et al.  (1993) An osmosensing signal transduction pathway in yeast. Science 259(5102):1760-3
8) Posas F and Saito H  (1997) Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK. Science 276(5319):1702-5
9) Westfall PJ, et al.  (2004) When the stress of your environment makes you go HOG wild. Science 306(5701):1511-2
10) Shiozaki K and Russell P  (1995) Counteractive roles of protein phosphatase 2C (PP2C) and a MAP kinase kinase homolog in the osmoregulation of fission yeast. EMBO J 14(3):492-502
11) Clark KL, et al.  (1995) Constitutive activation of the Saccharomyces cerevisiae mating response pathway by a MAP kinase kinase from Candida albicans. Mol Gen Genet 249(6):609-21
12) Ichimura K, et al.  (1998) Isolation of ATMEKK1 (a MAP kinase kinase kinase)-interacting proteins and analysis of a MAP kinase cascade in Arabidopsis. Biochem Biophys Res Commun 253(2):532-43
13) Kawasaki M, et al.  (1999) A Caenorhabditis elegans JNK signal transduction pathway regulates coordinated movement via type-D GABAergic motor neurons. EMBO J 18(13):3604-15
14) Kosako H, et al.  (1993) cDNA cloning of MAP kinase kinase reveals kinase cascade pathways in yeasts to vertebrates. EMBO J 12(2):787-94
15) Derijard B, et al.  (1995) Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science 267(5198):682-5
16) Maeda T, et al.  (1995) Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor. Science 269(5223):554-8
17) Tatebayashi K, et al.  (2003) A docking site determining specificity of Pbs2 MAPKK for Ssk2/Ssk22 MAPKKKs in the yeast HOG pathway. EMBO J 22(14):3624-34
18) Schwartz MA and Madhani HD  (2004) Principles of MAP kinase signaling specificity in Saccharomyces cerevisiae. Annu Rev Genet 38():725-48
19) Saito H and Tatebayashi K  (2004) Regulation of the osmoregulatory HOG MAPK cascade in yeast. J Biochem (Tokyo) 136(3):267-72
20) Reiser V, et al.  (2000) Polarized localization of yeast Pbs2 depends on osmostress, the membrane protein Sho1 and Cdc42. Nat Cell Biol 2(9):620-7
21) Gustin MC, et al.  (1998) MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev 62(4):1264-300
22) Boguslawski G  (1992) PBS2, a yeast gene encoding a putative protein kinase, interacts with the RAS2 pathway and affects osmotic sensitivity of Saccharomyces cerevisiae. J Gen Microbiol 138(11):2425-32
23) Lai MH, et al.  (1997) Multiple copies of PBS2, MHP1 or LRE1 produce glucanase resistance and other cell wall effects in Saccharomyces cerevisiae. Yeast 13(3):199-213
24) Jiang L, et al.  (2004) 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 271(2):208-19