Gene Symbol: BCK1
Description: mitogen-activated protein kinase kinase kinase BCK1
Alias: LAS3, SAP3, SLK1, SSP31, mitogen-activated protein kinase kinase kinase BCK1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Heinisch J, Lorberg A, Schmitz H, Jacoby J. The protein kinase C-mediated MAP kinase pathway involved in the maintenance of cellular integrity in Saccharomyces cerevisiae. Mol Microbiol. 1999;32:671-80 pubmed
  2. Lockshon D, Olsen C, Brett C, Chertov A, Merz A, Lorenz D, et al. Rho signaling participates in membrane fluidity homeostasis. PLoS ONE. 2012;7:e45049 pubmed publisher
    ..This work provides the first evidence for the existence of a signaling pathway that enables eukaryotic cells to control membrane fluidity, a requirement for division, differentiation and environmental adaptation. ..
  3. 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
    ..This phenotypic defect is similar to that associated with deletion of the BCK1 gene, which is thought to function in the pathway mediated by PCK1...
  4. 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. ..
  5. 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. ..
  6. Lee K, Irie K, Gotoh Y, Watanabe Y, Araki H, Nishida E, et al. A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C. Mol Cell Biol. 1993;13:3067-75 pubmed
    ..MPK1 gene was isolated as a dosage-dependent suppressor of the cell lysis defect associated with deletion of the BCK1 gene...
  7. Leza M, Elion E. POG1, a novel yeast gene, promotes recovery from pheromone arrest via the G1 cyclin CLN2. Genetics. 1999;151:531-43 pubmed
    ..The block in transcriptional repression occurs at SCB/MCB promoter elements by a mechanism that requires Bck1 but not Cln3...
  8. Lee K, Levin D. Dominant mutations in a gene encoding a putative protein kinase (BCK1) bypass the requirement for a Saccharomyces cerevisiae protein kinase C homolog. Mol Cell Biol. 1992;12:172-82 pubmed
    ..of the suppressor mutations were dominant for suppressor function and defined a single locus, which was designated BCK1 (for bypass of C kinase)...
  9. 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. ..

More Information


  1. Madden K, Sheu Y, Baetz K, Andrews B, Snyder M. SBF cell cycle regulator as a target of the yeast PKC-MAP kinase pathway. Science. 1997;275:1781-4 pubmed
    ..These studies provide evidence for a direct role of the PKC1 pathway in the regulation of the yeast cell cycle and cell growth and indicate that conserved signaling pathways can act to control key regulators of cell division. ..
  2. 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. ..
  3. Ketela T, Green R, Bussey H. Saccharomyces cerevisiae mid2p is a potential cell wall stress sensor and upstream activator of the PKC1-MPK1 cell integrity pathway. J Bacteriol. 1999;181:3330-40 pubmed
    ..In addition, we have identified an open reading frame, MTL1, which encodes a protein with both structural and functional similarity to Mid2p. ..
  4. Nunez L, Jesch S, Gaspar M, Almaguer C, Villa Garcia M, Ruiz Noriega M, et al. Cell wall integrity MAPK pathway is essential for lipid homeostasis. J Biol Chem. 2008;283:34204-17 pubmed publisher
    ..These results indicate that an intact cell wall integrity pathway is required for maintaining proper lipid homeostasis in yeast, especially when cells are grown in the absence of inositol. ..
  5. Nakamura T, Ohmoto T, Hirata D, Tsuchiya E, Miyakawa T. Yeast Crv4/Ttp1, a predicted type II membrane protein, is involved in an event important for growth, functionally overlapping with the event regulated by calcineurin- and Mpk1-mediated pathways. Mol Gen Genet. 1997;256:481-7 pubmed
    ..These results indicate that Ttp1 participates in a cellular event essential for growth and morphogenesis, in parallel with the pathways involving Mpk1 MAP kinase and calcineurin. ..
  6. 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
    ..Multicopy expression 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...
  7. Zanelli C, Valentini S. Pkc1 acts through Zds1 and Gic1 to suppress growth and cell polarity defects of a yeast eIF5A mutant. Genetics. 2005;171:1571-81 pubmed
    ..Taken together, these data strongly support the correlated involvement of Pkc1 and eIF5A in establishing actin polarity, which is essential for bud formation and G1/S transition in S. cerevisiae. ..
  8. 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. ..
  9. Nickas M, Yaffe M. BRO1, a novel gene that interacts with components of the Pkc1p-mitogen-activated protein kinase pathway in Saccharomyces cerevisiae. Mol Cell Biol. 1996;16:2585-93 pubmed
    Yeast cells with mutations in BRO1 display phenotypes similar to those caused by deletion of BCK1, a gene encoding a MEK kinase that functions in a mitogen-activated protein kinase pathway mediating maintenance of cell integrity...
  10. Lorberg A, Jacoby J, Schmitz H, Heinisch J. The PH domain of the yeast GEF Rom2p serves an essential function in vivo. Mol Genet Genomics. 2001;266:505-13 pubmed
  11. Khalfan W, Ivanovska I, Rose M. Functional interaction between the PKC1 pathway and CDC31 network of SPB duplication genes. Genetics. 2000;155:1543-59 pubmed
    ..In support of the model that the PKC1 pathway regulates SPB duplication, one of the phosphorylated forms of Spc110p was absent in pkc1 and mpk1Delta mutants. ..
  12. Niles B, Powers T. TOR complex 2-Ypk1 signaling regulates actin polarization via reactive oxygen species. Mol Biol Cell. 2014;25:3962-72 pubmed publisher
  13. Stanger K, Gorelik M, Davidson A. Yeast adaptor protein, Nbp2p, is conserved regulator of fungal Ptc1p phosphatases and is involved in multiple signaling pathways. J Biol Chem. 2012;287:22133-41 pubmed publisher
    ..Our results also clearly imply a function for the Nbp2p-Ptc1p complex other cellular processes. ..
  14. Costigan C, Snyder M. SLK1, a yeast homolog of MAP kinase activators, has a RAS/cAMP-independent role in nutrient sensing. Mol Gen Genet. 1994;243:286-96 pubmed
    The Saccharomyces cerevisiae SLK1 protein is implicated in nutrient sensing and growth control. Under nutrient-limiting conditions, slk1 mutants fail to undergo cell cycle arrest...
  15. 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
    ..These results suggest that the members of the PKC1-mediated MAP kinase cascade form a complex in vivo and that Pkc1p is capable of directly interacting with at least one component of this pathway. ..
  16. 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. ..
  17. Turchini A, Ferrario L, Popolo L. Increase of external osmolarity reduces morphogenetic defects and accumulation of chitin in a gas1 mutant of Saccharomyces cerevisiae. J Bacteriol. 2000;182:1167-71 pubmed
    ..GAS1 deletion was found to be lethal in the absence of the Bck1 and Slt2 (Mpk1) proteins of the cell integrity pathway.
  18. 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
    ..We suggest that Ser(407) and Thr(411) are novel residues of Mkk1 activated by these MAPK pathways. ..
  19. 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
  20. 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
  21. Andrews P, Stark M. Type 1 protein phosphatase is required for maintenance of cell wall integrity, morphogenesis and cell cycle progression in Saccharomyces cerevisiae. J Cell Sci. 2000;113 ( Pt 3):507-20 pubmed
    ..Although neither activation of BCK1 (MEKK) by the dominant BCK1-20 mutation nor increased dosage of MKK1 (MEK) or MPK1 (MAP kinase) mimicked PKC1 as a ..
  22. Watanabe Y, Takaesu G, Hagiwara M, Irie K, Matsumoto K. Characterization of a serum response factor-like protein in Saccharomyces cerevisiae, Rlm1, which has transcriptional activity regulated by the Mpk1 (Slt2) mitogen-activated protein kinase pathway. Mol Cell Biol. 1997;17:2615-23 pubmed
    ..Overexpression of MLP1 suppresses the caffeine-sensitive phenotype of the bck1 delta mutation...
  23. Catala M, Aksouh L, Abou Elela S. RNA-dependent regulation of the cell wall stress response. Nucleic Acids Res. 2012;40:7507-17 pubmed publisher
    ..The data supports a model for gene regulation in which nuclear mRNA degradation optimizes the cell response to stress and links it to the cell cycle. ..
  24. Backhaus K, Rippert D, Heilmann C, Sorgo A, de Koster C, Klis F, et al. Mutations in SNF1 complex genes affect yeast cell wall strength. Eur J Cell Biol. 2013;92:383-95 pubmed publisher
    ..Epistasis analyses with mutants in cell wall integrity (CWI) signaling confirm that the SNF1 complex and the CWI pathway independently affect yeast cell integrity. ..
  25. Wang Y, Zhu M, Ayalew M, Ruff J. Down-regulation of Pkc1-mediated signaling by the deubiquitinating enzyme Ubp3. J Biol Chem. 2008;283:1954-61 pubmed
    ..Chem. 277, 15766-15772). These findings demonstrate that Ubp3 can regulate Pkc1 by facilitating its destruction and provide the initial evidence that Pkc1 plays a positive role in modulating the parallel pheromone-signaling pathway. ..
  26. 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
    ..This behavior suggests that Ste5p, which has been proposed to be a tether for the kinases in the mating pathway, contributes to Ste7p specificity. ..
  27. Zarzov P, Mazzoni C, Mann C. The SLT2(MPK1) MAP kinase is activated during periods of polarized cell growth in yeast. EMBO J. 1996;15:83-91 pubmed
    ..BCK1(SLK1), a MEK kinase, is required for SLT2 activation in both of these situations...
  28. Traven A, Lo T, Pike B, Friesen H, Guzzo J, Andrews B, et al. Dual functions of Mdt1 in genome maintenance and cell integrity pathways in Saccharomyces cerevisiae. Yeast. 2010;27:41-52 pubmed publisher
    ..leads to severe synthetic sickness in the absence of the genes for the central cell integrity MAP kinases Bck1 and Slt2/Mpk1...
  29. Schmitz H, Huppert S, Lorberg A, Heinisch J. Rho5p downregulates the yeast cell integrity pathway. J Cell Sci. 2002;115:3139-48 pubmed
    ..Kinetics of actin depolarisation and repolarisation after heat treatment of rho5 deletions as well as strains overexpressing the activated RHO5Q91H allele provide further evidence for such a function. ..
  30. Varelas X, Stuart D, Ellison M, Ptak C. The Cdc34/SCF ubiquitination complex mediates Saccharomyces cerevisiae cell wall integrity. Genetics. 2006;174:1825-39 pubmed
    ..Given the differential roles that these GAPs play in the regulation of Rho1, these observations indicate the importance of coordinating Cdc34/SCF activity with specific Rho1 functions. ..
  31. 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
  32. Ragni E, Piberger H, Neupert C, García Cantalejo J, Popolo L, Arroyo J, et al. The genetic interaction network of CCW12, a Saccharomyces cerevisiae gene required for cell wall integrity during budding and formation of mating projections. BMC Genomics. 2011;12:107 pubmed publisher
    ..Among those are BCK1, CHS3, EDE1, PFD1, SLT2 and SLA1 that were also identified in the SGA...
  33. Luo G, Costanzo M, Boone C, Dickson R. Nutrients and the Pkh1/2 and Pkc1 protein kinases control mRNA decay and P-body assembly in yeast. J Biol Chem. 2011;286:8759-70 pubmed publisher
    ..Mammals may use similar regulatory mechanisms because components of the decay apparatus and signaling pathways are conserved. ..
  34. Fujiwara T, Tanaka K, Mino A, Kikyo M, Takahashi K, Shimizu K, et al. Rho1p-Bni1p-Spa2p interactions: implication in localization of Bni1p at the bud site and regulation of the actin cytoskeleton in Saccharomyces cerevisiae. Mol Biol Cell. 1998;9:1221-33 pubmed
    ..These results indicate that both Rho1p and Spa2p are involved in the localization of Bni1p at the growth sites where Rho1p regulates reorganization of the actin cytoskeleton through Bni1p. ..
  35. Claret S, Gatti X, Doignon F, Thoraval D, Crouzet M. The Rgd1p Rho GTPase-activating protein and the Mid2p cell wall sensor are required at low pH for protein kinase C pathway activation and cell survival in Saccharomyces cerevisiae. Eukaryot Cell. 2005;4:1375-86 pubmed
    ..Here, we show that this pathway mediates tolerance to low pH and that the Bck1 and Slt2 proteins belonging to the mitogen-activated protein kinase cascade are essential for cell survival at low ..
  36. Santos B, Snyder M. Sbe2p and sbe22p, two homologous Golgi proteins involved in yeast cell wall formation. Mol Biol Cell. 2000;11:435-52 pubmed
    ..Thus, we suggest a model in which Sbe2p and Sbe22p are involved in the transport of cell wall components from the Golgi apparatus to the cell surface periphery in a pathway independent of Chs5p. ..
  37. 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
  38. 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
  39. Petkova M, Pujol Carrion N, Arroyo J, García Cantalejo J, Angeles de la Torre Ruiz M. Mtl1 is required to activate general stress response through Tor1 and Ras2 inhibition under conditions of glucose starvation and oxidative stress. J Biol Chem. 2010;285:19521-31 pubmed publisher
    ..These mechanisms would be required to allow cells to adapt to both oxidative and nutritional stresses. ..
  40. Gorelik M, Davidson A. Distinct peptide binding specificities of Src homology 3 (SH3) protein domains can be determined by modulation of local energetics across the binding interface. J Biol Chem. 2012;287:9168-77 pubmed publisher
    ..Remarkably, this modulation of local binding energetics can explain the distinct and highly nuanced binding specificities of these two domains. ..
  41. Levin D, Bowers B, Chen C, Kamada Y, Watanabe M. Dissecting the protein kinase C/MAP kinase signalling pathway of Saccharomyces cerevisiae. Cell Mol Biol Res. 1994;40:229-39 pubmed
    ..Consistent with the proposed model, Pkc1p selectively phosphorylates Bck1p in vitro and Mpk1p protein kinase activity requires a functional BCK1 gene.
  42. Nakamura T, Ohmoto T, Hirata D, Tsuchiya E, Miyakawa T. Genetic evidence for the functional redundancy of the calcineurin- and Mpk1-mediated pathways in the regulation of cellular events important for growth in Saccharomyces cerevisiae. Mol Gen Genet. 1996;251:211-9 pubmed
    ..CRV3 genes which complemented the crv2 and crv3 mutations, respectively, are identical to those of BCK1/SLK1/SKC1/SSP31 and MPK1/SLT2, respectively, which are both involved in the MAP kinase cascade...
  43. Tomishige N, Noda Y, Adachi H, Shimoi H, Takatsuki A, Yoda K. Mutations that are synthetically lethal with a gas1Delta allele cause defects in the cell wall of Saccharomyces cerevisiae. Mol Genet Genomics. 2003;269:562-73 pubmed
    ..Furthermore, the genes CSG2 and IPT1 were found to be required for normal growth of gas1Delta cells in the presence of 1 M sorbitol. This finding suggests that complex sphingolipids play a role in the hyper-osmotic response. ..
  44. Costigan C, Gehrung S, Snyder M. A synthetic lethal screen identifies SLK1, a novel protein kinase homolog implicated in yeast cell morphogenesis and cell growth. Mol Cell Biol. 1992;12:1162-78 pubmed
    ..One mutant, called slk-1 (for synthetic lethal kinase), has been characterized extensively. The SLK1 gene has been cloned, and sequence analysis predicts that the SLK1 protein is 1,478 amino acid residues in length...
  45. Cohen T, Mallory M, Strich R, Yao T. Hos2p/Set3p deacetylase complex signals secretory stress through the Mpk1p cell integrity pathway. Eukaryot Cell. 2008;7:1191-9 pubmed publisher
  46. Lenburg M, O Shea E. Genetic evidence for a morphogenetic function of the Saccharomyces cerevisiae Pho85 cyclin-dependent kinase. Genetics. 2001;157:39-51 pubmed
    ..are previously identified genes-BEM2 (YER155C), SPT7 (YBR081C), GCR1 (YPL075W), SRB5 (YGR104C), HFI1 (YPL254W), and BCK1 (YJL095W)-with one novel gene (YMR212C)...
  47. Jacoby J, Nilius S, Heinisch J. A screen for upstream components of the yeast protein kinase C signal transduction pathway identifies the product of the SLG1 gene. Mol Gen Genet. 1998;258:148-55 pubmed
    We employed the constitutive BCK1-20 allele of the gene for the MAP kinase kinase kinase (MAP-KKK) in the yeast Pkc signal transduction pathway to develop a genetic screen for mutants in genes encoding upstream components...
  48. Tigano M, Ruotolo R, Dallabona C, Fontanesi F, Barrientos A, Donnini C, et al. Elongator-dependent modification of cytoplasmic tRNALysUUU is required for mitochondrial function under stress conditions. Nucleic Acids Res. 2015;43:8368-80 pubmed publisher
    ..deficiency was selectively rescued by overexpression of tRNA(Lys) UUU as well by overexpression of genes (BCK1 and HFM1) with a strong bias for the AAA codon read by this tRNA...
  49. 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
    ..Lack of Sch9p alleviates the phenotype of slt2? and bck1? mutant cells, as well as attenuation of PKA activity by overexpression of BCY1 (bypass of cyclase mutations 1)...
  50. Chen Y, Feldman D, Deng C, Brown J, De Giacomo A, Gaw A, et al. Identification of mitogen-activated protein kinase signaling pathways that confer resistance to endoplasmic reticulum stress in Saccharomyces cerevisiae. Mol Cancer Res. 2005;3:669-77 pubmed
    ..We propose that the SLT2 MAPK pathway is an important cell survival signaling pathway during ER stress. This study shows the feasibility of using the yeast deletion pool to identify relevant mammalian orthologues of the UPR. ..
  51. Shen Z, Li Y, Gasparski A, Abeliovich H, Greenberg M. Cardiolipin Regulates Mitophagy through the Protein Kinase C Pathway. J Biol Chem. 2017;292:2916-2923 pubmed publisher
    ..These findings indicate that loss of CL impairs MAPK pathway activation, and decreased activation of the PKC pathway leads to defective mitophagy. ..
  52. Tabuchi M, Audhya A, Parsons A, Boone C, Emr S. The phosphatidylinositol 4,5-biphosphate and TORC2 binding proteins Slm1 and Slm2 function in sphingolipid regulation. Mol Cell Biol. 2006;26:5861-75 pubmed
    ..Together, our data suggest that Slm1 and Slm2 define a molecular link between phosphoinositide and sphingolipid signaling and thereby regulate actin cytoskeleton organization. ..