Gene Symbol: wis1
Description: MAP kinase kinase Wis1
Alias: smf2, spc2, MAP kinase kinase Wis1
Species: fission yeast

Top Publications

  1. Shiozaki K, Russell P. Cell-cycle control linked to extracellular environment by MAP kinase pathway in fission yeast. Nature. 1995;378:739-43 pubmed
    ..Spc1 is a MAP kinase homologue that is activated by Wis1 kinase in response to osmotic stress and nutrient limitation...
  2. Degols G, Shiozaki K, Russell P. Activation and regulation of the Spc1 stress-activated protein kinase in Schizosaccharomyces pombe. Mol Cell Biol. 1996;16:2870-7 pubmed
    ..Spc1, also known as Sty1, is activated by Wis1 MAPK kinase and inhibited by Pyp1 tyrosine phosphatase...
  3. Wilkinson M, Samuels M, Takeda T, Toone W, Shieh J, Toda T, et al. The Atf1 transcription factor is a target for the Sty1 stress-activated MAP kinase pathway in fission yeast. Genes Dev. 1996;10:2289-301 pubmed
    ..de novo protein synthesis and results in a negative feedback loop that serves to control signaling through the Sty1/Wis1 pathway. We show that Atf1 associates stably and is phosphorylated by the Sty1 kinase in vitro...
  4. Samejima I, Mackie S, Warbrick E, Weisman R, Fantes P. The fission yeast mitotic regulator win1+ encodes an MAP kinase kinase kinase that phosphorylates and activates Wis1 MAP kinase kinase in response to high osmolarity. Mol Biol Cell. 1998;9:2325-35 pubmed
    ..Although the defect is suppressed by wis1+ and wis4+, which are components of a stress-activated MAP kinase pathway that links stress response and cell cycle ..
  5. Kato T, Okazaki K, Murakami H, Stettler S, Fantes P, Okayama H. Stress signal, mediated by a Hog1-like MAP kinase, controls sexual development in fission yeast. FEBS Lett. 1996;378:207-12 pubmed
    We identified the phh1+ gene that encodes a MAP kinase as the effector of Wis1 MAP kinase kinase in fission yeast, which is highly homologous with HOG1 of S. cerevisiae...
  6. Shiozaki K, Russell P. Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast. Genes Dev. 1996;10:2276-88 pubmed
    The stress-activated Wis1-Spc1 protein kinase cascade links mitotic control with environmental signals in Schizosaccharomyces pombe...
  7. Samejima I, Mackie S, Fantes P. Multiple modes of activation of the stress-responsive MAP kinase pathway in fission yeast. EMBO J. 1997;16:6162-70 pubmed
    The Schizosaccharomyces pombe wis1(+) gene is essential for cell survival under stress conditions...
  8. Nguyen A, Lee A, Place W, Shiozaki K. Multistep phosphorelay proteins transmit oxidative stress signals to the fission yeast stress-activated protein kinase. Mol Biol Cell. 2000;11:1169-81 pubmed
    ..These studies show that oxidative stress stimuli are transmitted by multiple pathways to induce specific gene expression. ..
  9. Shieh J, Wilkinson M, Buck V, Morgan B, Makino K, Millar J. The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle. Genes Dev. 1997;11:1008-22 pubmed
    ..Mcs4 acts upstream of Wak1, a homolog of the SSK2 and SSK22 MEK kinases, which transmits the stress signal to the Wis1 MEK...

More Information


  1. Wang L, Shimada K, Morishita M, Shiozaki K. Response of fission yeast to toxic cations involves cooperative action of the stress-activated protein kinase Spc1/Sty1 and the Hal4 protein kinase. Mol Cell Biol. 2005;25:3945-55 pubmed
    ..Strains lacking Spc1 or its activator, Wis1 MAPK kinase, are hypersensitive to these cations...
  2. Gaits F, Degols G, Shiozaki K, Russell P. Phosphorylation and association with the transcription factor Atf1 regulate localization of Spc1/Sty1 stress-activated kinase in fission yeast. Genes Dev. 1998;12:1464-73 pubmed
    ..Nuclear translocation of Spc1 is coupled with disassociation from its activator kinase Wis1. However, Spc1 does not concentrate in the nucleus of Deltawis1 cells; therefore Wis1 does not tether Spc1 in the ..
  3. Shieh J, Wilkinson M, Millar J. The Win1 mitotic regulator is a component of the fission yeast stress-activated Sty1 MAPK pathway. Mol Biol Cell. 1998;9:311-22 pubmed
    The fission yeast Sty1 mitogen-activated protein (MAP) kinase (MAPK) and its activator the Wis1 MAP kinase kinase (MAPKK) are required for cell cycle control, initiation of sexual differentiation, and protection against cellular stress...
  4. Nguyen A, Shiozaki K. Heat-shock-induced activation of stress MAP kinase is regulated by threonine- and tyrosine-specific phosphatases. Genes Dev. 1999;13:1653-63 pubmed
    ..Although osmostress and oxidative stress induce strong activation of the Wis1 MAPK kinase (MEK), which activates Spc1 through Thr-171/Tyr-173 phosphorylation, activation of Wis1 upon heat shock ..
  5. Tatebe H, Shiozaki K. Identification of Cdc37 as a novel regulator of the stress-responsive mitogen-activated protein kinase. Mol Cell Biol. 2003;23:5132-42 pubmed
    ..the cdc37 mutation affects both the cellular level of the Spc1 protein and stress-induced Spc1 phosphorylation by Wis1 MAPK kinase (MAPKK)...
  6. Millar J, Buck V, Wilkinson M. Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast. Genes Dev. 1995;9:2117-30 pubmed
    ..We find that sty2 is allelic to the wis1 MAP kinase kinase and that delta sty1 and delta wis1 cells are unable to grow in high osmolarity medium...
  7. Weisman R, Roitburg I, Nahari T, Kupiec M. Regulation of leucine uptake by tor1+ in Schizosaccharomyces pombe is sensitive to rapamycin. Genetics. 2005;169:539-50 pubmed
    ..These findings suggest a possible mechanism for regulation of leucine uptake by tor1p and indicate that tor1p, as well as tsc1p and tsc2p, positively regulates leucine uptake in S. pombe. ..
  8. Shieh J, Martin H, Millar J. Evidence for a novel MAPKKK-independent pathway controlling the stress activated Sty1/Spc1 MAP kinase in fission yeast. J Cell Sci. 1998;111 ( Pt 18):2799-807 pubmed
    ..Sty1 is activated by a single MAPKK, Wis1. We demonstrate that the conserved MAPKKK phosphorylation sites Ser 469 and Thr 473 in the catalytic domain of Wis1 ..
  9. Stiefel J, Wang L, Kelly D, Janoo R, Seitz J, Whitehall S, et al. Suppressors of an adenylate cyclase deletion in the fission yeast Schizosaccharomyces pombe. Eukaryot Cell. 2004;3:610-9 pubmed
    ..that reduce high-level fbp1+ transcription conferred by the loss of adenylate cyclase (git2delta), including both wis1- (SAPK kinase) and spc1- (SAPK) mutants...
  10. Nakashima A, Hasegawa T, Mori S, Ueno M, Tanaka S, Ushimaru T, et al. A starvation-specific serine protease gene, isp6+, is involved in both autophagy and sexual development in Schizosaccharomyces pombe. Curr Genet. 2006;49:403-13 pubmed
    ..These observations suggest that isp6(+) contributes to sexual development by providing a nitrogen source through autophagy. ..
  11. Sengar A, Markley N, Marini N, Young D. Mkh1, a MEK kinase required for cell wall integrity and proper response to osmotic and temperature stress in Schizosaccharomyces pombe. Mol Cell Biol. 1997;17:3508-19 pubmed
    ..Our results also suggest that Mkh1 and Pck2 act independently to maintain cell wall integrity, cell morphology, and salt resistance but act in opposition to regulate filamentous growth. ..
  12. Sukegawa Y, Yamashita A, Yamamoto M. The fission yeast stress-responsive MAPK pathway promotes meiosis via the phosphorylation of Pol II CTD in response to environmental and feedback cues. PLoS Genet. 2011;7:e1002387 pubmed publisher
    ..phosphorylation increases under nitrogen starvation, and the stress-responsive MAP kinase pathway, mediated by Wis1 MAPKK and Sty1 MAPK, is critical for this stress response...
  13. Sanchez Piris M, Posas F, Alemany V, Winge I, Hidalgo E, Bachs O, et al. The serine/threonine kinase Cmk2 is required for oxidative stress response in fission yeast. J Biol Chem. 2002;277:17722-7 pubmed
    ..Cell lethality caused by overexpression of Wis1 MAPK kinase was abolished by deletion of cmk2 or by mutation of Thr-411 of Cmk2...
  14. Jang Y, Won M, Yoo H. Phosphorylations of Sds23/Psp1/Moc1 by stress-activated kinase and cAMP-dependent kinase are essential for regulating cell viability in prolonged stationary phase. Yeast. 2013;30:379-94 pubmed publisher
  15. Di Y, Holmes E, Butt A, Dawson K, Mironov A, Kotiadis V, et al. H?O? stress-specific regulation of S. pombe MAPK Sty1 by mitochondrial protein phosphatase Ptc4. EMBO J. 2012;31:563-75 pubmed publisher
  16. Janoo R, Neely L, Braun B, Whitehall S, Hoffman C. Transcriptional regulators of the Schizosaccharomyces pombe fbp1 gene include two redundant Tup1p-like corepressors and the CCAAT binding factor activation complex. Genetics. 2001;157:1205-15 pubmed
    ..Deletion of php5 reduces fbp1 expression under both repressed and derepressed conditions. The CBF appears to act in parallel to atf1-pcr1, although it is unclear whether or not CBF activity is regulated by PKA. ..
  17. Nguyen A, Ikner A, Shiozaki M, Warren S, Shiozaki K. Cytoplasmic localization of Wis1 MAPKK by nuclear export signal is important for nuclear targeting of Spc1/Sty1 MAPK in fission yeast. Mol Biol Cell. 2002;13:2651-63 pubmed
    ..Herein, we show that the Wis1 MAPKK of the stress-activated Spc1 MAPK cascade in fission yeast also has a MAPK-docking site and an NES sequence ..
  18. Morigasaki S, Shiozaki K. Phosphorelay-dependent and -independent regulation of MAPKKK by the Mcs4 response regulator in fission yeast. Commun Integr Biol. 2013;6:e25020 pubmed publisher
    ..The Mcs4 RR may serve as a switching hub that mediates activation of the Wis4-Win1 MAPKKK heteromer in response to different forms of stress. ..
  19. Aiba H, Yamada H, Ohmiya R, Mizuno T. The osmo-inducible gpd1+ gene is a target of the signaling pathway involving Wis1 MAP-kinase kinase in fission yeast. FEBS Lett. 1995;376:199-201 pubmed
    ..pombe is under the control of a MAP-signaling pathway involving the wis1+ gene-product, which is a homologue of MAP-kinase kinases...
  20. Rodríguez Gabriel M, Russell P. Distinct signaling pathways respond to arsenite and reactive oxygen species in Schizosaccharomyces pombe. Eukaryot Cell. 2005;4:1396-402 pubmed
    ..mitogen-activated protein kinase (MAPK), a homologue of mammalian p38 MAPK, and the upstream MAPK kinase (MAPKK) Wis1 are essential for survival of both arsenite and hydrogen peroxide...
  21. Vázquez B, Soto T, del Dedo J, Franco A, Vicente J, Hidalgo E, et al. Distinct biological activity of threonine monophosphorylated MAPK isoforms during the stress response in fission yeast. Cell Signal. 2015;27:2534-42 pubmed publisher
    ..Thus, threonine monophosphorylated MAPKs might display distinct functional relevance among eukaryotes. ..
  22. Stettler S, Warbrick E, Prochnik S, Mackie S, Fantes P. The wis1 signal transduction pathway is required for expression of cAMP-repressed genes in fission yeast. J Cell Sci. 1996;109 ( Pt 7):1927-35 pubmed
    The wis1 protein kinase of Schizosaccharomyces pombe is a member of the MAP kinase kinase family...
  23. Shiozaki K, Russell P. Counteractive roles of protein phosphatase 2C (PP2C) and a MAP kinase kinase homolog in the osmoregulation of fission yeast. EMBO J. 1995;14:492-502 pubmed
    ..One locus is identical to wis1+, encoding a MAP kinase kinase (MEK) homolog...
  24. Smith D, Toone W, Chen D, Bahler J, Jones N, Morgan B, et al. The Srk1 protein kinase is a target for the Sty1 stress-activated MAPK in fission yeast. J Biol Chem. 2002;277:33411-21 pubmed
  25. Kanoh J, Russell P. The protein kinase Cdr2, related to Nim1/Cdr1 mitotic inducer, regulates the onset of mitosis in fission yeast. Mol Biol Cell. 1998;9:3321-34 pubmed
    ..Thus, Cdr2 is a novel mitotic control protein that appears to regulate Wee1...
  26. Toone W, Kuge S, Samuels M, Morgan B, Toda T, Jones N. Regulation of the fission yeast transcription factor Pap1 by oxidative stress: requirement for the nuclear export factor Crm1 (Exportin) and the stress-activated MAP kinase Sty1/Spc1. Genes Dev. 1998;12:1453-63 pubmed
    ..This relocalization is the result of regulated protein export, rather than import, and involves the Crm1 (exportin) nuclear export factor and the dcd1+/pim1+ gene that encodes an Ran nucleotide exchange factor. ..
  27. Kawasaki Y, Nagao K, Nakamura T, Yanagida M. Fission yeast MAP kinase is required for the increased securin-separase interaction that rescues separase mutants under stresses. Cell Cycle. 2006;5:1831-9 pubmed
    ..Securin bound to separase was hyperphosphorylated. The stresses could not rescue the indestructible Cut2 and Rad21 mutants. We postulate that the stresses produce the hyperchaperonic form of Cut2 that can rescue separase mutations. ..
  28. Caspari T. Onset of gluconate-H+ symport in Schizosaccharomyces pombe is regulated by the kinases Wis1 and Pka1, and requires the gti1+ gene product. J Cell Sci. 1997;110 ( Pt 20):2599-608 pubmed
    ..Moreover, inactivation of the stress-sensing Wis1-Sty1 MAP kinase pathway, by loss of Wis1 MAP kinase kinase, diminishes 10-fold the onset of gluconate uptake in ..
  29. Warbrick E, Fantes P. The wis1 protein kinase is a dosage-dependent regulator of mitosis in Schizosaccharomyces pombe. EMBO J. 1991;10:4291-9 pubmed
    The wis1+ gene encodes a newly identified mitotic control element in Schizosaccharomyces pombe. It was isolated by virtue of its interaction with the mitotic control genes cdc25, wee1 and win1...
  30. Toda T, Niwa H, Nemoto T, Dhut S, Eddison M, Matsusaka T, et al. The fission yeast sts5+ gene is required for maintenance of growth polarity and functionally interacts with protein kinase C and an osmosensing MAP-kinase pathway. J Cell Sci. 1996;109 ( Pt 9):2331-42 pubmed
    ..Consistent with this, we have found that the wis1 mutation, which is defective in a MAP-kinase kinase of the pathway, suppresses the sts5 mutation...
  31. Morigasaki S, Ikner A, Tatebe H, Shiozaki K. Response regulator-mediated MAPKKK heteromer promotes stress signaling to the Spc1 MAPK in fission yeast. Mol Biol Cell. 2013;24:1083-92 pubmed publisher
    ..The Wis4-Win1 complex discovered in fission yeast demonstrates that heteromer-mediated mechanisms are not limited to mammalian MAPKKKs. ..