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Gene Review

SLT2  -  mitogen-activated serine/threonine-protein...

Saccharomyces cerevisiae S288c

Synonyms: BYC2, LYT2, MAP kinase MPK1, MPK1, Mitogen-activated protein kinase SLT2/MPK1, ...
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Disease relevance of SLT2


High impact information on SLT2

  • Sir3p phosphorylation by the Slt2p pathway effects redistribution of silencing function and shortened lifespan [4].
  • Thus, Slt2p is an enzymatic regulator of silencing function that couples commitment to cell growth and shorter lifespan [4].
  • Role of calcineurin and Mpk1 in regulating the onset of mitosis in budding yeast [5].
  • Calcineurin and Mpk1 regulate Swel activation at the transcriptional and posttranslational levels, respectively, and both are required for the calcium-induced delay in G2 phase [5].
  • We show that the PKC1-regulated pathway is important for induced thermotolerance and that the MPK1 protein kinase (the MAPK of this pathway) is strongly activated by mild heat shock [6].

Biological context of SLT2

  • The SLT2 (MPK1) MAP kinase homolog is involved in polarized cell growth in Saccharomyces cerevisiae [7].
  • We show that slt2 mutants exhibit phenotypes similar to those shown by mutants of the yeast actin cytoskeleton, including delocalization of chitin deposition and of actin cortical spots and the accumulation of secretory pathway membranes and vesicles [7].
  • The protein kinase C of Saccharomyces cerevisiae, Pkc1, regulates a MAP kinase, Mpk1, whose activity is stimulated at the G1-S transition of the cell cycle and by perturbations to the cell surface, e.g. induced by heat shock [8].
  • The MPK1 gene possesses a 1.5-kb uninterrupted open reading frame predicted to encode a 53-kDa protein [9].
  • To search for genes that interact with the Mpk1 pathway, we isolated both chromosomal mutations and dosage suppressor genes that ameliorate the growth-inhibitory effect of overexpressed Mkk1P386 [10].

Anatomical context of SLT2


Associations of SLT2 with chemical compounds

  • Deletion of the MPK1/SLT2 gene disturbs the glucose-triggered K(m) decrease in ATPase [15].
  • Mutation of the presumptive phosphorylated tyrosine and threonine residues of Mpk1p individually to phenylalanine and alanine, respectively, severely impaired Mpk1p function [9].
  • In contrast, the Slt2p C-terminal domain (162 residues) that carries a glutamine-rich fragment followed by a 16 polyglutamine tract, was shown to be dispensable for complementation and in vivo association with Mkk1p and Mkk2p [16].
  • Overexpression of SIW14 also rescued the caffeine sensitivity of the slt2 mutant isolated in the screen, but this was not due to alteration of the phosphorylation state of Slt2 [17].
  • A role for MID2 in the cell integrity pathway is further supported by the finding that MID2 is required for induction of Mpk1p tyrosine phosphorylation during exposure to alpha-factor, calcofluor white, or high temperature [18].

Physical interactions of SLT2

  • In this paper, we demonstrate by two-hybrid, in vitro immunoprecipitation and tandem affinity purification (TAP) methods that Knr4p physically interacts with Slt2p [19].
  • Consistent with a role of this phosphatase on cell wall physiology, cells lacking Msg5 displayed an increased sensitivity to the cell wall-interfering compound Congo Red. We have observed that the N-terminal non-catalytic region of this phosphatase was responsible for binding to the kinase domain of Slt2, the MAPK that operates in this pathway [20].

Enzymatic interactions of SLT2

  • Ptp2 was more efficient than Ptp3 at binding and dephosphorylating Mpk1 [21].
  • Reciprocally, Slt2 phosphorylated Msg5 as a consequence of the activation of the cell integrity pathway [20].
  • The Mpk1 MAP kinase of the Saccharomyces cerevisiae cell wall integrity signalling pathway phosphorylates and activates the Rlm1 transcription factor in response to cell wall stress [22].

Regulatory relationships of SLT2

  • The defect in recovery of the delta cnb1 mutant was suppressed by overexpression of MPK1 [23].
  • Furthermore, overexpression of the Pkc1-controlled mitogen-activated protein (MAP) kinase Mpk1 suppressed the actin defect of tor2ts and rho1-2ts mutants [24].
  • Cdc42-induced activation of Slt2 occurs in a mating and filamentation pathway-dependent manner, but it does not require the function of Rho1, which is the GTPase that operates in the cell integrity pathway [1].
  • Moreover, the expression of genes previously identified as targets of the Mpk1 pathway are also up-regulated in strains lacking PPZ1 and -2 [25].
  • Calcineurin and Mpk1 activate Swe1 at the transcriptional and post-translational level, respectively, and both pathways are essential for the cell cycle delay [26].

Other interactions of SLT2

  • We suggest that Slt2p functions downstream or in parallel with Cdc28p in promoting bud formation and apical growth [7].
  • Our results suggest that Rlm1 functions as a transcription factor downstream of Mpk1 that is subject to activation by the Mpk1 mitogen-activated protein kinase pathway [10].
  • The MPK1 gene was isolated as a dosage-dependent suppressor of the cell lysis defect associated with deletion of the BCK1 gene [9].
  • Transcriptional coregulation by the cell integrity mitogen-activated protein kinase Slt2 and the cell cycle regulator Swi4 [11].
  • Expression of Xenopus MAP kinase suppressed the defect associated with loss of MPK1 but not the mating-related defects associated with loss of FUS3 or KSS1, indicating functional conservation between the former two protein kinases [9].

Analytical, diagnostic and therapeutic context of SLT2


  1. A novel connection between the yeast Cdc42 GTPase and the Slt2-mediated cell integrity pathway identified through the effect of secreted Salmonella GTPase modulators. Rodríguez-Pachón, J.M., Martín, H., North, G., Rotger, R., Nombela, C., Molina, M. J. Biol. Chem. (2002) [Pubmed]
  2. The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function. Kraus, P.R., Fox, D.S., Cox, G.M., Heitman, J. Mol. Microbiol. (2003) [Pubmed]
  3. Regulation of the oxidative stress response through Slt2p-dependent destruction of cyclin C in Saccharomyces cerevisiae. Krasley, E., Cooper, K.F., Mallory, M.J., Dunbrack, R., Strich, R. Genetics (2006) [Pubmed]
  4. Sir3p phosphorylation by the Slt2p pathway effects redistribution of silencing function and shortened lifespan. Ray, A., Hector, R.E., Roy, N., Song, J.H., Berkner, K.L., Runge, K.W. Nat. Genet. (2003) [Pubmed]
  5. Role of calcineurin and Mpk1 in regulating the onset of mitosis in budding yeast. Mizunuma, M., Hirata, D., Miyahara, K., Tsuchiya, E., Miyakawa, T. Nature (1998) [Pubmed]
  6. The protein kinase C-activated MAP kinase pathway of Saccharomyces cerevisiae mediates a novel aspect of the heat shock response. Kamada, Y., Jung, U.S., Piotrowski, J., Levin, D.E. Genes Dev. (1995) [Pubmed]
  7. The SLT2 (MPK1) MAP kinase homolog is involved in polarized cell growth in Saccharomyces cerevisiae. Mazzoni, C., Zarov, P., Rambourg, A., Mann, C. J. Cell Biol. (1993) [Pubmed]
  8. A role for the Pkc1 MAP kinase pathway of Saccharomyces cerevisiae in bud emergence and identification of a putative upstream regulator. Gray, J.V., Ogas, J.P., Kamada, Y., Stone, M., Levin, D.E., Herskowitz, I. EMBO J. (1997) [Pubmed]
  9. A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C. Lee, K.S., Irie, K., Gotoh, Y., Watanabe, Y., Araki, H., Nishida, E., Matsumoto, K., Levin, D.E. Mol. Cell. Biol. (1993) [Pubmed]
  10. Yeast RLM1 encodes a serum response factor-like protein that may function downstream of the Mpk1 (Slt2) mitogen-activated protein kinase pathway. Watanabe, Y., Irie, K., Matsumoto, K. Mol. Cell. Biol. (1995) [Pubmed]
  11. Transcriptional coregulation by the cell integrity mitogen-activated protein kinase Slt2 and the cell cycle regulator Swi4. Baetz, K., Moffat, J., Haynes, J., Chang, M., Andrews, B. Mol. Cell. Biol. (2001) [Pubmed]
  12. Role for lipid signaling and the cell integrity MAP kinase cascade in yeast septum biogenesis. Tahirovic, S., Schorr, M., Then, A., Berger, J., Schwarz, H., Mayinger, P. Curr. Genet. (2003) [Pubmed]
  13. Spa2p functions as a scaffold-like protein to recruit the Mpk1p MAP kinase module to sites of polarized growth. van Drogen, F., Peter, M. Curr. Biol. (2002) [Pubmed]
  14. Cell wall perturbation in yeast results in dual phosphorylation of the Slt2/Mpk1 MAP kinase and in an Slt2-mediated increase in FKS2-lacZ expression, glucanase resistance and thermotolerance. de Nobel, H., Ruiz, C., Martin, H., Morris, W., Brul, S., Molina, M., Klis, F.M. Microbiology (Reading, Engl.) (2000) [Pubmed]
  15. The cell wall integrity/remodeling MAPK cascade is involved in glucose activation of the yeast plasma membrane H(+)-ATPase. de la Fuente, N., Portillo, F. Biochim. Biophys. Acta (2000) [Pubmed]
  16. Characterization of domains in the yeast MAP kinase Slt2 (Mpk1) required for functional activity and in vivo interaction with protein kinases Mkk1 and Mkk2. Soler, M., Plovins, A., Martín, H., Molina, M., Nombela, C. Mol. Microbiol. (1995) [Pubmed]
  17. A synthetic lethal screen identifies a role for the cortical actin patch/endocytosis complex in the response to nutrient deprivation in Saccharomyces cerevisiae. Care, A., Vousden, K.A., Binley, K.M., Radcliffe, P., Trevethick, J., Mannazzu, I., Sudbery, P.E. Genetics (2004) [Pubmed]
  18. Saccharomyces cerevisiae mid2p is a potential cell wall stress sensor and upstream activator of the PKC1-MPK1 cell integrity pathway. Ketela, T., Green, R., Bussey, H. J. Bacteriol. (1999) [Pubmed]
  19. The interaction of Slt2 MAP kinase with Knr4 is necessary for signalling through the cell wall integrity pathway in Saccharomyces cerevisiae. Martin-Yken, H., Dagkessamanskaia, A., Basmaji, F., Lagorce, A., Francois, J. Mol. Microbiol. (2003) [Pubmed]
  20. Reciprocal regulation between Slt2 MAPK and isoforms of Msg5 dual-specificity protein phosphatase modulates the yeast cell integrity pathway. Flández, M., Cosano, I.C., Nombela, C., Martín, H., Molina, M. J. Biol. Chem. (2004) [Pubmed]
  21. Differential regulation of the cell wall integrity mitogen-activated protein kinase pathway in budding yeast by the protein tyrosine phosphatases Ptp2 and Ptp3. Mattison, C.P., Spencer, S.S., Kresge, K.A., Lee, J., Ota, I.M. Mol. Cell. Biol. (1999) [Pubmed]
  22. Regulation of the yeast Rlm1 transcription factor by the Mpk1 cell wall integrity MAP kinase. Jung, U.S., Sobering, A.K., Romeo, M.J., Levin, D.E. Mol. Microbiol. (2002) [Pubmed]
  23. 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. Nakamura, T., Ohmoto, T., Hirata, D., Tsuchiya, E., Miyakawa, T. Mol. Gen. Genet. (1996) [Pubmed]
  24. The Rho1 effector Pkc1, but not Bni1, mediates signalling from Tor2 to the actin cytoskeleton. Helliwell, S.B., Schmidt, A., Ohya, Y., Hall, M.N. Curr. Biol. (1998) [Pubmed]
  25. Response of the Saccharomyces cerevisiae Mpk1 mitogen-activated protein kinase pathway to increases in internal turgor pressure caused by loss of Ppz protein phosphatases. Merchan, S., Bernal, D., Serrano, R., Yenush, L. Eukaryotic Cell (2004) [Pubmed]
  26. GSK-3 kinase Mck1 and calcineurin coordinately mediate Hsl1 down-regulation by Ca2+ in budding yeast. Mizunuma, M., Hirata, D., Miyaoka, R., Miyakawa, T. EMBO J. (2001) [Pubmed]
  27. Molecular and functional characterization of a mutant allele of the mitogen-activated protein-kinase gene SLT2(MPK1) rescued from yeast autolytic mutants. Martín, H., Castellanos, M.C., Cenamor, R., Sánchez, M., Molina, M., Nombela, C. Curr. Genet. (1996) [Pubmed]
  28. Oxidative stress activates FUS1 and RLM1 transcription in the yeast Saccharomyces cerevisiae in an oxidant-dependent Manner. Staleva, L., Hall, A., Orlow, S.J. Mol. Biol. Cell (2004) [Pubmed]
  29. Protein-protein interactions in the yeast PKC1 pathway: Pkc1p interacts with a component of the MAP kinase cascade. Paravicini, G., Friedli, L. Mol. Gen. Genet. (1996) [Pubmed]
  30. Activity of the yeast MAP kinase homologue Slt2 is critically required for cell integrity at 37 degrees C. Martín, H., Arroyo, J., Sánchez, M., Molina, M., Nombela, C. Mol. Gen. Genet. (1993) [Pubmed]
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