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Gene Review

PKC1  -  protein kinase C

Saccharomyces cerevisiae S288c

Synonyms: CLY15, CLY5, CLY7, HPO2, PKC 1, ...
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Disease relevance of PKC1

  • The Saccharomyces cerevisiae cwh43-2 mutant, originally isolated for its Calcofluor white hypersensitivity, displays several cell wall defects similar to mutants in the PKC1-MPK1 pathway, including a growth defect and increased release of beta-1,6-glucan and beta-glucosylated proteins into the growth medium at increased temperatures [1].
  • The results of these analyses support our hypothesis that under heat stress conditions the activation of the PKC1 pathway is triggered by an increase in intracellular osmolarity, due to the accumulation of trehalose, rather than by the increase in temperature as such [2].
  • In this study, Pkc1p was modified at its COOH terminus with the influenza virus hemagglutinin epitope and was detected by SDS-polyacrylamide gel electrophoresis as a 145- and 150-kDa doublet when overproduced in yeast cells [3].
  • Pkc1p modified at its COOH terminus with two repeats of the Staphylococcus aureus protein A IgG-binding fragment (ZZ sequence tag) was able to fully restore the growth defects of a pkc1ts strain at restrictive temperature [4].
  • Using the mAb M7 against rat brain PKC, a single 70 kDa band was identified in total cell extracts of Bacillus subtilis by Western blotting after SDS-PAGE, whilst using polyclonal antibody alpha-PKC1p against Saccharomyces cerevisiae PKC a single 67 kDa band was identified by the same procedure [5].

High impact information on PKC1

  • Cells depleted of the PKC1 gene product displayed a uniform phenotype, a characteristic of cell division cycle (cdc) mutants, and arrested cell division at a point subsequent to DNA replication, but prior to mitosis [6].
  • A candidate protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle [6].
  • Experiments with a dominant positive PKC1 gene showed that the two effects of Rho1p are independent of each other [7].
  • 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 [8].
  • Expression of genes under the control of known heat shock-inducible promoter elements (HSEs and STREs) was not compromised in PKC1 pathway mutants, indicating that this pathway mediates a novel aspect of the yeast heat shock response [8].

Chemical compound and disease context of PKC1


Biological context of PKC1

  • These phenotypes are partially suppressed by overexpression of upstream elements of the protein kinase C (PKC1) cell integrity pathway, suggesting that the PKC1 pathway is defective in pmt2 pmt4Delta mutants [10].
  • The PKC1 gene of Saccharomyces cerevisiae encodes a homolog of mammalian protein kinase C that is required for yeast cell growth [11].
  • The PKC1 gene has been proposed to regulate a bifurcated pathway, on one branch of which function four putative protein kinases that catalyze a linear cascade of protein phosphorylation culminating in the activation of the mitogen-activated protein kinase homolog, Mpk1p [11].
  • Reduced O mannosylation leads to incorrect proteolytic processing of these proteins, which in turn results in impaired activation of the PKC1 pathway and finally causes cell death in the absence of osmotic stabilization [10].
  • Overexpression of multiple PKC1 pathway components suppressed the G2/M arrest of the SPB duplication mutants and mutations in MPK1 exacerbated the cell cycle arrest of kar1-Delta17, suggesting a role for the PKC1 pathway in SPB duplication [12].

Anatomical context of PKC1


Associations of PKC1 with chemical compounds

  • In budding yeast, PKC1 plays an essential role in cell integrity and proliferation through a linear MAP (Mitogen Activated Protein) kinase phosphorylation cascade, which ends up with the activation of the Slt2-MAP kinase by dual phosphorylation on two conserved threonine and tyrosine residues [16].
  • The overexpression of PKC1, however, did not suppress the HU sensitivity of Deltampt5 [17].
  • These suppression and synthetic lethal interactions, as well as reduced beta-glucan and mannan levels in the pkc1 null wall, support a role for the PKC1 pathway functioning in cell wall assembly [18].
  • Integration of the glucan interaction network with the caspofungin data indicates an overlapping set of genes involved in FKS2 regulation, compensatory chitin synthesis, protein mannosylation, and the PKC1-dependent cell integrity pathway [19].
  • This cell lysis defect can be rescued by adding osmotic stabilizers, such as 1 M sorbitol, to the medium, and by overexpressing PKC1 or RHO1 [20].

Physical interactions of PKC1

  • 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 [21].
  • KNR4 is a member of the PKC1 signalling pathway and genetically interacts with BCK2, a gene involved in cell cycle progression in Saccharomyces cerevisiae [22].

Enzymatic interactions of PKC1


Regulatory relationships of PKC1

  • The dominant activating mutation of PKC1 suppressed the temperature sensitivity of two effector mutants of RHO1, rho1(F44Y) and rho1(E451), but not that of rho1(V43T) [21].
  • The growth and budding defects of swi4 mutants are suppressed by overexpression of PKC1 [25].
  • The PKC1 gene in the yeast Saccharomyces cerevisiae encodes protein kinase C that is known to control a mitogen-activated protein (MAP) kinase cascade consisting of Bck1, Mkk1 and Mkk2, and Mpk1 [26].
  • Significantly, growth in the presence of 1 M sorbitol or overexpression of PKC1 also partially suppresses the lethal phenotype of the sds3 swi6 strain [27].
  • This suggests that the PKC1 kinase cascade regulates BGL2 expression negatively and overproduction of the beta-glucanase is partially responsible for the growth defect.(ABSTRACT TRUNCATED AT 250 WORDS)[28]
  • 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 [29].

Other interactions of PKC1

  • 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 [25].
  • These results indicate that there are at least two signaling pathways regulated by Rho1p and that one of the downstream targets is Pkc1p, leading to the activation of the MAP kinase cascade [21].
  • The activity of the Pkc1 pathway is partially dependent on Cdc28 activity [25].
  • Inhibition of the Pkc1 pathway exacerbates the growth and bud emergence defects of swi4 mutants [25].
  • MKK1 and MPK1 encode MAP kinase kinase and MAP kinase homologs, respectively, and function downstream of PKC1 [21].

Analytical, diagnostic and therapeutic context of PKC1

  • Sequence analysis revealed that the complementing DNA fragment encoded a partial PKC1 gene, which has previously been isolated as an S. cerevisiae homolog of mammalian protein kinase C genes (D. E. Levin, F. O. Fields, R. Kunisawa, J. M. Bishop, and J. Thorner, Cell 62:213-224, 1990) [30].
  • Sequence alignment shows that AIP1 is highly similar to BRO1, a yeast protein related to components of the Pkc1p-MAP kinase cascade [31].
  • Early in the cell cycle, Pkc1p-GFP was found at the pre-bud site and bud tips, becoming delocalized as the cell progressed further and finally relocalizing around the mother-daughter bud neck in an incomplete ring, which persisted until cell separation [32].
  • Using fungal genomic DNA as template and primers targeted to conserved sequences in the Saccharomyces cerevisiae pkc1 gene, two partially overlapping extra long polymerase chain reaction (XL-PCR) products were obtained [33].


  1. Saccharomyces cerevisiae YCRO17c/CWH43 encodes a putative sensor/transporter protein upstream of the BCK2 branch of the PKC1-dependent cell wall integrity pathway. Martin-Yken, H., Dagkessamanskaia, A., De Groot, P., Ram, A., Klis, F., François, J. Yeast (2001) [Pubmed]
  2. Activation of the protein kinase C1 pathway upon continuous heat stress in Saccharomyces cerevisiae is triggered by an intracellular increase in osmolarity due to trehalose accumulation. Mensonides, F.I., Brul, S., Klis, F.M., Hellingwerf, K.J., Teixeira de Mattos, M.J. Appl. Environ. Microbiol. (2005) [Pubmed]
  3. Saccharomyces cerevisiae PKC1 encodes a protein kinase C (PKC) homolog with a substrate specificity similar to that of mammalian PKC. Watanabe, M., Chen, C.Y., Levin, D.E. J. Biol. Chem. (1994) [Pubmed]
  4. Protein kinase C in yeast. Characteristics of the Saccharomyces cerevisiae PKC1 gene product. Antonsson, B., Montessuit, S., Friedli, L., Payton, M.A., Paravicini, G. J. Biol. Chem. (1994) [Pubmed]
  5. Purification of two Bacillus subtilis proteins which cross-react with antibodies directed against eukaryotic protein kinase C, the His HPr kinase and trigger factor. Zouari, N., Roche, B., Seegers, J.F., Séror, S. Microbiology (Reading, Engl.) (1997) [Pubmed]
  6. A candidate protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle. Levin, D.E., Fields, F.O., Kunisawa, R., Bishop, J.M., Thorner, J. Cell (1990) [Pubmed]
  7. Rho1p, a yeast protein at the interface between cell polarization and morphogenesis. Drgonová, J., Drgon, T., Tanaka, K., Kollár, R., Chen, G.C., Ford, R.A., Chan, C.S., Takai, Y., Cabib, E. Science (1996) [Pubmed]
  8. 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]
  9. Mutations in WSC genes for putative stress receptors result in sensitivity to multiple stress conditions and impairment of Rlm1-dependent gene expression in Saccharomyces cerevisiae. Zu, T., Verna, J., Ballester, R. Mol. Genet. Genomics (2001) [Pubmed]
  10. Aberrant processing of the WSC family and Mid2p cell surface sensors results in cell death of Saccharomyces cerevisiae O-mannosylation mutants. Lommel, M., Bagnat, M., Strahl, S. Mol. Cell. Biol. (2004) [Pubmed]
  11. A pair of functionally redundant yeast genes (PPZ1 and PPZ2) encoding type 1-related protein phosphatases function within the PKC1-mediated pathway. Lee, K.S., Hines, L.K., Levin, D.E. Mol. Cell. Biol. (1993) [Pubmed]
  12. Functional interaction between the PKC1 pathway and CDC31 network of SPB duplication genes. Khalfan, W., Ivanovska, I., Rose, M.D. Genetics (2000) [Pubmed]
  13. Yeast RSC function is required for organization of the cellular cytoskeleton via an alternative PKC1 pathway. Chai, B., Hsu, J.M., Du, J., Laurent, B.C. Genetics (2002) [Pubmed]
  14. PKC1, a protein kinase C homologue of Saccharomyces cerevisiae, participates in microtubule function through the yeast EB1 homologue, BIM1. Hosotani, T., Koyama, H., Uchino, M., Miyakawa, T., Tsuchiya, E. Genes Cells (2001) [Pubmed]
  15. Regulation of organelle membrane fusion by Pkc1p. Lin, A., Patel, S., Latterich, M. Traffic (2001) [Pubmed]
  16. 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]
  17. Suppressor analysis of the mpt5/htr1/uth4/puf5 deletion in Saccharomyces cerevisiae. Ohkuni, K., Kikuchi, Y., Hara, K., Taneda, T., Hayashi, N., Kikuchi, A. Mol. Genet. Genomics (2006) [Pubmed]
  18. Characterization of the yeast (1-->6)-beta-glucan biosynthetic components, Kre6p and Skn1p, and genetic interactions between the PKC1 pathway and extracellular matrix assembly. Roemer, T., Paravicini, G., Payton, M.A., Bussey, H. J. Cell Biol. (1994) [Pubmed]
  19. Analysis of beta-1,3-glucan assembly in Saccharomyces cerevisiae using a synthetic interaction network and altered sensitivity to caspofungin. Lesage, G., Sdicu, A.M., Ménard, P., Shapiro, J., Hussein, S., Bussey, H. Genetics (2004) [Pubmed]
  20. A novel role for the mating type (MAT) locus in the maintenance of cell wall integrity in Saccharomyces cerevisiae. Verna, J., Ballester, R. Mol. Gen. Genet. (1999) [Pubmed]
  21. 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. Nonaka, H., Tanaka, K., Hirano, H., Fujiwara, T., Kohno, H., Umikawa, M., Mino, A., Takai, Y. EMBO J. (1995) [Pubmed]
  22. KNR4 is a member of the PKC1 signalling pathway and genetically interacts with BCK2, a gene involved in cell cycle progression in Saccharomyces cerevisiae. Martin-Yken, H., Dagkessamanskaia, A., Talibi, D., Francois, J. Curr. Genet. (2002) [Pubmed]
  23. Sphingoid base signaling via Pkh kinases is required for endocytosis in yeast. Friant, S., Lombardi, R., Schmelzle, T., Hall, M.N., Riezman, H. EMBO J. (2001) [Pubmed]
  24. Regulation of yeast CTP synthetase activity by protein kinase C. Yang, W.L., Bruno, M.E., Carman, G.M. J. Biol. Chem. (1996) [Pubmed]
  25. 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]
  26. Evidence for involvement of Saccharomyces cerevisiae protein kinase C in glucose induction of HXT genes and derepression of SUC2. Brandão, R.L., Etchebehere, L., Queiroz, C.C., Trópia, M.J., Ernandes, J.R., Gonçalves, T., Loureiro-Dias, M.C., Winderickx, J., Thevelein, J.M., Leiper, F.C., Carling, D., Castro, I.M. FEMS Yeast Res. (2002) [Pubmed]
  27. A role for Sds3p, a component of the Rpd3p/Sin3p deacetylase complex, in maintaining cellular integrity in Saccharomyces cerevisiae. Vannier, D., Damay, P., Shore, D. Mol. Genet. Genomics (2001) [Pubmed]
  28. The hypo-osmolarity-sensitive phenotype of the Saccharomyces cerevisiae hpo2 mutant is due to a mutation in PKC1, which regulates expression of beta-glucanase. Shimizu, J., Yoda, K., Yamasaki, M. Mol. Gen. Genet. (1994) [Pubmed]
  29. Down-regulation of Pkc1-mediated signaling by the deubiquitinating enzyme Ubp3. Wang, Y., Zhu, M., Ayalew, M., Ruff, J.A. J. Biol. Chem. (2008) [Pubmed]
  30. The osmotic integrity of the yeast cell requires a functional PKC1 gene product. Paravicini, G., Cooper, M., Friedli, L., Smith, D.J., Carpentier, J.L., Klig, L.S., Payton, M.A. Mol. Cell. Biol. (1992) [Pubmed]
  31. Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction. Vito, P., Pellegrini, L., Guiet, C., D'Adamio, L. J. Biol. Chem. (1999) [Pubmed]
  32. Dynamic, Rho1p-dependent localization of Pkc1p to sites of polarized growth. Andrews, P.D., Stark, M.J. J. Cell. Sci. (2000) [Pubmed]
  33. Characterization of a protein kinase C gene in Sporothrix schenckii and its expression during the yeast-to-mycelium transition. Aquino-Piñero, E., Rodríguez-del Valle, N. Med. Mycol. (2002) [Pubmed]
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