Gene Symbol: SSK2
Description: mitogen-activated protein kinase kinase kinase SSK2
Alias: mitogen-activated protein kinase kinase kinase SSK2
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. 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. ..
  2. 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
    ..extracellular osmolarity induces the HOG1 mitogen-activated protein kinase (MAPK) cascade, which is composed of SSK2, SSK22 and STE11 MAPKKKs, PBS2 MAPKK and HOG1 MAPK...
  3. Yuzyuk T, Amberg D. Actin recovery and bud emergence in osmotically stressed cells requires the conserved actin interacting mitogen-activated protein kinase kinase kinase Ssk2p/MTK1 and the scaffold protein Spa2p. Mol Biol Cell. 2003;14:3013-26 pubmed
    ..Polarized Ssk2p associates with the scaffold protein Spa2p in the bud and Shs1p in the neck, allowing Ssk2p to regulate substrates involved in polarized actin assembly. ..
  4. 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
    ..The Ssk2/Ssk22 MAPKKKs in the SLN1 branch, when activated, exclusively phosphorylate the Pbs2 MAPKK...
  5. 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. ..
  6. Horie T, Tatebayashi K, Yamada R, Saito H. Phosphorylated Ssk1 prevents unphosphorylated Ssk1 from activating the Ssk2 mitogen-activated protein kinase kinase kinase in the yeast high-osmolarity glycerol osmoregulatory pathway. Mol Cell Biol. 2008;28:5172-83 pubmed publisher
    ..Ssk1 is a homolog of bacterial two-component response regulators and activates the Ssk2 MAPK kinase kinase upstream of Hog1...
  7. 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. ..
  8. 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
    ..Alternatively, Pbs2p was activated by a mechanism that involves the binding of its amino terminal proline-rich motif to the Src homology 3 (SH3) domain of a putative transmembrane osmosensor Sho1p. ..
  9. 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. ..

More Information


  1. Yuzyuk T, Foehr M, Amberg D. The MEK kinase Ssk2p promotes actin cytoskeleton recovery after osmotic stress. Mol Biol Cell. 2002;13:2869-80 pubmed
    ..These unique capabilities of Ssk2p are activated by a novel mechanism that does not involve known components of the HOG pathway. ..
  2. Raitt D, Posas F, Saito H. Yeast Cdc42 GTPase and Ste20 PAK-like kinase regulate Sho1-dependent activation of the Hog1 MAPK pathway. EMBO J. 2000;19:4623-31 pubmed
    ..Since activated Cdc42 translocates Ste20 to sites of polarized growth, the upstream and downstream elements of the HOG pathway are brought together through the membrane targeting function of Sho1 and Cdc42. ..
  3. Singh K. The Saccharomyces cerevisiae Sln1p-Ssk1p two-component system mediates response to oxidative stress and in an oxidant-specific fashion. Free Radic Biol Med. 2000;29:1043-50 pubmed
    ..These results suggest that Sln1p-Ssk1p and Sho1p signal transduction pathways participate in oxidative stress response. However, this response to oxidative stress is limited to specific oxidants. ..
  4. Warmka J, Hanneman J, Lee J, Amin D, Ota I. Ptc1, a type 2C Ser/Thr phosphatase, inactivates the HOG pathway by dephosphorylating the mitogen-activated protein kinase Hog1. Mol Cell Biol. 2001;21:51-60 pubmed
    ..Consistent with its role as a negative regulator of Hog1, which accumulates in the nucleus upon activation, Ptc1 was found in both the nucleus and the cytoplasm. Thus, one function of Ptc1 is to inactivate Hog1. ..
  5. Rep M, Reiser V, Gartner U, Thevelein J, Hohmann S, Ammerer G, et al. Osmotic stress-induced gene expression in Saccharomyces cerevisiae requires Msn1p and the novel nuclear factor Hot1p. Mol Cell Biol. 1999;19:5474-85 pubmed
    ..Thus, Hot1p and Msn1p may define an additional tier of transcriptional regulators that control responses to high-osmolarity stress. ..
  6. Jiang L, Cao C, Zhang L, Lin W, Xia J, Xu H, et al. Cadmium-induced activation of high osmolarity glycerol pathway through its Sln1 branch is dependent on the MAP kinase kinase kinase Ssk2, but not its paralog Ssk22, in budding yeast. FEMS Yeast Res. 2014;14:1263-72 pubmed publisher
    ..Cadmium-induced HOG activation is dependent on the MAP kinase kinase kinase Ssk2, but not its paralog Ssk22, in the Sln1 branch.
  7. Gomar Alba M, Alepuz P, del Olmo M. Dissection of the elements of osmotic stress response transcription factor Hot1 involved in the interaction with MAPK Hog1 and in the activation of transcription. Biochim Biophys Acta. 2013;1829:1111-25 pubmed publisher
    ..Moreover, both sequences are required for osmotolerance and KR4 is necessary for the functionality of the HOG pathway. According to several experiments described in this study, the Hot1 protein is capable of forming homodimers. ..
  8. 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
    ..Together, these data suggest that the V-ATPase acts in parallel with the HOG pathway in order to mediate salt detoxification. ..
  9. 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
    ..Thus, the kinase activity of Hog1p is required for its own tyrosine dephosphorylation. Northern blot analyses suggest that Hog1p regulates Ptp2p and/or Ptp3p activity at the posttranscriptional level. ..
  10. Sharifian H, Lampert F, Stojanovski K, Regot S, Vaga S, Buser R, et al. Parallel feedback loops control the basal activity of the HOG MAPK signaling cascade. Integr Biol (Camb). 2015;7:412-22 pubmed publisher
    ..Indeed, we found that Hog1 phosphorylates its activating kinase Ssk2 on several sites, and cells expressing a non-phosphorylatable Ssk2 mutant are partially defective for feedback ..
  11. Zhi H, Tang L, Xia Y, Zhang J. Ssk1p-independent activation of Ssk2p plays an important role in the osmotic stress response in Saccharomyces cerevisiae: alternative activation of Ssk2p in osmotic stress. PLoS ONE. 2013;8:e54867 pubmed publisher
    ..MAPKKK Ssk2 is activated by Ssk1 in the SLN1 branch of the osmoregulatory HOG MAPK pathway under hyperosmotic stress...
  12. Hermansyah -, Laviña W, Sugiyama M, Kaneko Y, Harashima S. Identification of protein kinase disruptions as suppressors of the calcium sensitivity of S. cerevisiae Deltaptp2 Deltamsg5 protein phosphatase double disruptant. Arch Microbiol. 2010;192:157-65 pubmed publisher
  13. 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. ..
  14. Macia J, Regot S, Peeters T, Conde N, Solé R, Posas F. Dynamic signaling in the Hog1 MAPK pathway relies on high basal signal transduction. Sci Signal. 2009;2:ra13 pubmed publisher
    ..Analysis of two other yeast MAPK pathways, the Fus3 and Kss1 signaling pathways, indicates that high intrinsic basal signaling may be a general property of MAPK pathways allowing rapid and sensitive responses to environmental changes. ..
  15. Hawle P, Horst D, Bebelman J, Yang X, Siderius M, van der Vies S. Cdc37p is required for stress-induced high-osmolarity glycerol and protein kinase C mitogen-activated protein kinase pathway functionality by interaction with Hog1p and Slt2p (Mpk1p). Eukaryot Cell. 2007;6:521-32 pubmed
    ..Interestingly, phosphorylated Slt2p, but not phosphorylated Hog1p, has an increased affinity for Cdc37p. Together these observations suggest that Cdc37p acts as a regulator of MAPK signaling. ..
  16. Posas F, Witten E, Saito H. Requirement of STE50 for osmostress-induced activation of the STE11 mitogen-activated protein kinase kinase kinase in the high-osmolarity glycerol response pathway. Mol Cell Biol. 1998;18:5788-96 pubmed
    ..HOG1 mitogen-activated protein (MAP) kinase cascade, which is composed of three tiers of protein kinases: (i) the SSK2, SSK22, and STE11 MAP kinase kinase kinases (MAPKKKs), (ii) the PBS2 MAPKK, and (iii) the HOG1 MAP kinase...
  17. Wojda I, Alonso Monge R, Bebelman J, Mager W, Siderius M. Response to high osmotic conditions and elevated temperature in Saccharomyces cerevisiae is controlled by intracellular glycerol and involves coordinate activity of MAP kinase pathways. Microbiology. 2003;149:1193-204 pubmed
    ..The data taken together indicate the intricate interdependence of growth temperature, intracellular glycerol, cell wall structure and MAP kinase signalling in the hyperosmotic stress response of yeast. ..
  18. 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
    ..In addition, the isolated multicopy suppressor genes suppress temperature-induced cell lysis phenotypes of PKC pathway mutants that could be an indication for shared targets of the PKC pathway and high-osmolarity response routes. ..
  19. Thorsen M, Di Y, Tängemo C, Morillas M, Ahmadpour D, Van der Does C, et al. The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast. Mol Biol Cell. 2006;17:4400-10 pubmed
    ..Understanding how arsenite/antimonite uptake and toxicity is modulated may prove of value for their use in medical therapy. ..
  20. 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
    ..In addition, the Pbs2 scaffold bound the Nbp2 SH3 via a Pro-rich motif distinct from that which binds the SH3 domain of the positive regulator Sho1. Thus, Nbp2 recruits Ptc1 to Pbs2, a scaffold for both negative and positive regulators. ..
  21. 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
    ..Finally, we have found that pseudohyphal growth exhibited by wild-type (HOG1) strains depends on SHO1, suggesting that Sho1p may be a receptor that feeds into the pseudohyphal growth pathway. ..