Gene Symbol: MKK1
Description: mitogen-activated protein kinase kinase MKK1
Alias: SSP32, mitogen-activated protein kinase kinase MKK1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Irie K, Takase M, Lee K, Levin D, Araki H, Matsumoto K, et al. MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase-kinase homologs, function in the pathway mediated by protein kinase C. Mol Cell Biol. 1993;13:3076-83 pubmed
    ..We report here the isolation of the yeast MKK1 and MKK2 (for mitogen-activated protein [MAP] kinase-kinase) genes which, when overexpressed, suppress the cell ..
  2. Watanabe Y, Irie K, Matsumoto K. Yeast RLM1 encodes a serum response factor-like protein that may function downstream of the Mpk1 (Slt2) mitogen-activated protein kinase pathway. Mol Cell Biol. 1995;15:5740-9 pubmed
    ..homolog of protein kinase C), Bck1 (Slk1) (a homolog of MEK kinase), and the functionally redundant Mpk1 activators Mkk1 and Mkk2 (homologs of MEK). An activated mutation of MKK1, MKK1P386, inhibits growth when overexpressed...
  3. Jimenez Sanchez M, Cid V, Molina M. Retrophosphorylation of Mkk1 and Mkk2 MAPKKs by the Slt2 MAPK in the yeast cell integrity pathway. J Biol Chem. 2007;282:31174-85 pubmed
    ..MAPK module lies downstream of the Rho1 small GTPase and protein kinase C Pkc1 and consists of MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the Slt2 MAPK...
  4. Hahn J, Thiele D. Regulation of the Saccharomyces cerevisiae Slt2 kinase pathway by the stress-inducible Sdp1 dual specificity phosphatase. J Biol Chem. 2002;277:21278-84 pubmed
    ..Deletion of SDP1 exacerbated growth defects due to overexpression of Mkk1(p386), a constitutively active mutant of Slt2 MAPK kinase, whereas overexpression of Sdp1 suppressed lethality ..
  5. Nonaka H, Tanaka K, Hirano H, Fujiwara T, Kohno H, Umikawa M, et al. A downstream target of RHO1 small GTP-binding protein is PKC1, a homolog of protein kinase C, which leads to activation of the MAP kinase cascade in Saccharomyces cerevisiae. EMBO J. 1995;14:5931-8 pubmed
    ..b>MKK1 and MPK1 encode MAP kinase kinase and MAP kinase homologs, respectively, and function downstream of PKC1...
  6. Harrison J, Bardes E, Ohya Y, Lew D. A role for the Pkc1p/Mpk1p kinase cascade in the morphogenesis checkpoint. Nat Cell Biol. 2001;3:417-20 pubmed
    ..The G2 delay involves stabilization of Swe1p in response to various actin perturbations, although this alone is insufficient to produce a long G2 delay. ..
  7. Schmelzle T, Helliwell S, Hall M. Yeast protein kinases and the RHO1 exchange factor TUS1 are novel components of the cell integrity pathway in yeast. Mol Cell Biol. 2002;22:1329-39 pubmed
    ..Furthermore, our findings suggest that the YPKs are a missing link between sphingolipid signaling and the cell integrity pathway. ..
  8. van Drogen F, Peter M. Spa2p functions as a scaffold-like protein to recruit the Mpk1p MAP kinase module to sites of polarized growth. Curr Biol. 2002;12:1698-703 pubmed
    ..Taken together, these results suggest that Spa2p functions as a scaffold-like protein for the cell wall integrity pathway during polarized growth. ..
  9. Sheu Y, Santos B, Fortin N, Costigan C, Snyder M. Spa2p interacts with cell polarity proteins and signaling components involved in yeast cell morphogenesis. Mol Cell Biol. 1998;18:4053-69 pubmed
    ..We thus propose that Spa2p, Pea2p, and Bud6p function together, perhaps as a complex, to promote polarized morphogenesis through regulation of the actin cytoskeleton and signaling pathways. ..

More Information


  1. Roemer T, Vallier L, Sheu Y, Snyder M. The Spa2-related protein, Sph1p, is important for polarized growth in yeast. J Cell Sci. 1998;111 ( Pt 4):479-94 pubmed
    ..Our results indicate that Spa2p and Sph1p comprise two related proteins important for the control of cell morphogenesis in yeast. ..
  2. Matia González A, Rodríguez Gabriel M. Slt2 MAPK pathway is essential for cell integrity in the presence of arsenate. Yeast. 2011;28:9-17 pubmed publisher
    ..Furthermore, our results support the idea that cellular exposure to arsenate results in induction of cellular signalling pathways different from those induced under arsenite treatment...
  3. de Bettignies G, Thoraval D, Morel C, Peypouquet M, Crouzet M. Overactivation of the protein kinase C-signaling pathway suppresses the defects of cells lacking the Rho3/Rho4-GAP Rgd1p in Saccharomyces cerevisiae. Genetics. 2001;159:1435-48 pubmed
    ..RHO1 and RHO2 encoding two small GTPases, MKK1 encoding one of the MAP-kinase kinases in the protein kinase C (PKC) pathway, and MTL1, a MID2-homolog, were shown ..
  4. Soler M, Plovins A, Martin H, Molina M, Nombela C. Characterization of domains in the yeast MAP kinase Slt2 (Mpk1) required for functional activity and in vivo interaction with protein kinases Mkk1 and Mkk2. Mol Microbiol. 1995;17:833-42 pubmed
    b>MKK1/MKK2 and SLT2 (MPK1) are three Saccharomyces cerevisiae genes, coding for protein kinases, that have been postulated to act sequentially as part of the Pkc1p signalling pathway, a phosphorylation cascade essential for cell integrity...
  5. Yashar B, Irie K, Printen J, Stevenson B, Sprague G, Matsumoto K, et al. Yeast MEK-dependent signal transduction: response thresholds and parameters affecting fidelity. Mol Cell Biol. 1995;15:6545-53 pubmed
    ..We selected STE7 and MKK1 mutations that stimulated their respective pathways in the absence of an inductive signal...
  6. Goshen Lago T, Goldberg Carp A, Melamed D, Darlyuk Saadon I, Bai C, Ahn N, et al. Variants of the yeast MAPK Mpk1 are fully functional independently of activation loop phosphorylation. Mol Biol Cell. 2016;27:2771-83 pubmed publisher
    ..Cells lacking MPK1, or the genes encoding the relevant MEKs, MKK1 and MKK2, do not proliferate under cell wall stress, imposed, for example, by caffeine...
  7. Tatjer L, Sacristán Reviriego A, Casado C, González A, Rodríguez Porrata B, Palacios L, et al. Wide-Ranging Effects of the Yeast Ptc1 Protein Phosphatase Acting Through the MAPK Kinase Mkk1. Genetics. 2016;202:141-56 pubmed publisher
    ..genes able to suppress multiple phenotypic traits caused by the ptc1 deletion yielded a single gene, MKK1, coding for a MAPK kinase (MAPKK) known to activate the cell-wall integrity (CWI) Slt2 MAPK...
  8. Helliwell S, Schmidt A, Ohya Y, Hall M. The Rho1 effector Pkc1, but not Bni1, mediates signalling from Tor2 to the actin cytoskeleton. Curr Biol. 1998;8:1211-4 pubmed
    ..Thus, Tor2 signals to the actin cytoskeleton via Rho1, Pkc1 and the cell integrity MAP kinase cascade. ..
  9. Merchan S, Pedelini L, Hueso G, Calzada A, Serrano R, Yenush L. Genetic alterations leading to increases in internal potassium concentrations are detrimental for DNA integrity in Saccharomyces cerevisiae. Genes Cells. 2011;16:152-65 pubmed publisher
  10. Levin Salomon V, Kogan K, Ahn N, Livnah O, Engelberg D. Isolation of intrinsically active (MEK-independent) variants of the ERK family of mitogen-activated protein (MAP) kinases. J Biol Chem. 2008;283:34500-10 pubmed publisher
    ..Thus, a first generation of Erk molecules that are spontaneously active in vitro and in vivo has been obtained. ..
  11. Ho H, Shiau Y, Chen M. Saccharomyces cerevisiaeTSC11/AVO3 participates in regulating cell integrity and functionally interacts with components of the Tor2 complex. Curr Genet. 2005;47:273-88 pubmed
  12. Mattison C, Spencer S, Kresge K, Lee J, Ota I. Differential regulation of the cell wall integrity mitogen-activated protein kinase pathway in budding yeast by the protein tyrosine phosphatases Ptp2 and Ptp3. Mol Cell Biol. 1999;19:7651-60 pubmed
    ..of PTP2, but not PTP3, suppressed growth defects due to the MEK kinase mutation, BCK1-20, and the MEK mutation, MKK1-386, that hyperactivate this pathway...
  13. Navarro Garcia F, Alonso Monge R, Rico H, Pla J, Sentandreu R, Nombela C. A role for the MAP kinase gene MKC1 in cell wall construction and morphological transitions in Candida albicans. Microbiology. 1998;144 ( Pt 2):411-24 pubmed
    ..cerevisiae when bound to a DNA-binding element. These results suggest a role for this MAP kinase in the construction of the cell wall of C. albicans and indicate its potential relevance for the development of novel antifungals. ..
  14. Harrison J, Zyla T, Bardes E, Lew D. Stress-specific activation mechanisms for the "cell integrity" MAPK pathway. J Biol Chem. 2004;279:2616-22 pubmed
    ..These findings suggest that stresses provide "lateral" inputs into this regulatory pathway, rather than operating in a linear "top-down" manner. ..
  15. Guo S, Shen X, Yan G, Ma D, Bai X, Li S, et al. A MAP kinase dependent feedback mechanism controls Rho1 GTPase and actin distribution in yeast. PLoS ONE. 2009;4:e6089 pubmed publisher
    ..It is also required for terminating Rho1 activity toward the Pkc1-MAPK pathway and for repolarizing actin cytoskeleton and restoring growth after the stressed cells become adapted. ..
  16. Zhao C, Jung U, Garrett Engele P, Roe T, Cyert M, Levin D. Temperature-induced expression of yeast FKS2 is under the dual control of protein kinase C and calcineurin. Mol Cell Biol. 1998;18:1013-22 pubmed
    ..Two components of the cell integrity signaling pathway controlled by the RHO1 G protein (MKK1 and RLM1) were identified through this screen...
  17. Li X, Ferro Novick S, Novick P. Different polarisome components play distinct roles in Slt2p-regulated cortical ER inheritance in Saccharomyces cerevisiae. Mol Biol Cell. 2013;24:3145-54 pubmed publisher
    ..Our results point to a common mechanism for the regulation of ER inheritance in which Slt2p activity at the bud tip controls the association of the ER with the actin-based cytoskeleton...
  18. Ohkuni K, Okuda A, Kikuchi A. Yeast Nap1-binding protein Nbp2p is required for mitotic growth at high temperatures and for cell wall integrity. Genetics. 2003;165:517-29 pubmed
    ..Ptc1, which interacts with Nbp2 by the two-hybrid system, acts downstream of Nbp2 and that cells lacking the function of Nbp2 prefer to lose Mkk1, but the PKC MAPK pathway itself is indispensable when Nbp2 is deleted at high temperature.
  19. Manjithaya R, Jain S, Farre J, Subramani S. A yeast MAPK cascade regulates pexophagy but not other autophagy pathways. J Cell Biol. 2010;189:303-10 pubmed publisher
    ..We propose that pexophagy requires the simultaneous activation of this MAPK pathway and a hexose-sensing mechanism acting through protein kinase A and cyclic adenosine monophosphate. ..
  20. Paravicini G, Friedli L. Protein-protein interactions in the yeast PKC1 pathway: Pkc1p interacts with a component of the MAP kinase cascade. Mol Gen Genet. 1996;251:682-91 pubmed
    ..Four positive clones were isolated that encoded portions of the protein kinase Mkk1, which acts downstream of Pkc1p in the PKC1-mediated signalling pathway...
  21. Palacios L, Dickinson R, Sacristán Reviriego A, Didmon M, Marin M, Martín H, et al. Distinct docking mechanisms mediate interactions between the Msg5 phosphatase and mating or cell integrity mitogen-activated protein kinases (MAPKs) in Saccharomyces cerevisiae. J Biol Chem. 2011;286:42037-50 pubmed publisher
    ..In contrast, Slt2 uses its CD domain to bind to its upstream activator Mkk1. This binding flexibility may allow MAPK pathways to exploit additional regulatory controls in order to provide ..
  22. Córcoles Sáez I, Ballester Tomás L, de la Torre Ruiz M, Prieto J, Randez Gil F. Low temperature highlights the functional role of the cell wall integrity pathway in the regulation of growth in Saccharomyces cerevisiae. Biochem J. 2012;446:477-88 pubmed publisher
    ..Hence, cold signalling through the CWI pathway has distinct features and might mediate still unknown effectors and targets. ..
  23. Leng G, Song K. Direct interaction of Ste11 and Mkk1/2 through Nst1 integrates high-osmolarity glycerol and pheromone pathways to the cell wall integrity MAPK pathway. FEBS Lett. 2016;590:148-60 pubmed publisher
    ..Here, we identify a new interaction of Ste11 and Mkk1, mediated by Nst1 that connects the high-osmolarity glycerol and pheromone pathways directly to CWI pathway in ..
  24. McDaniel S, Hepperla A, Huang J, Dronamraju R, Adams A, Kulkarni V, et al. H3K36 Methylation Regulates Nutrient Stress Response in Saccharomyces cerevisiae by Enforcing Transcriptional Fidelity. Cell Rep. 2017;19:2371-2382 pubmed publisher
    ..These results suggest that Set2-enforced transcriptional fidelity is critical to the proper regulation of inducible and highly regulated transcription programs. ..