This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sun, Y.
Right arrow Articles by Kozutsumi, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, Y.
Right arrow Articles by Kozutsumi, Y.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2000, p. 4411-4419, Vol. 20, No. 12
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Sli2 (Ypk1), a Homologue of Mammalian Protein Kinase SGK, Is a Downstream Kinase in the Sphingolipid-Mediated Signaling Pathway of Yeast

Yidi Sun,1 Ritsuko Taniguchi,1 Daisuke Tanoue,2 Toshiyuki Yamaji,1 Hiromu Takematsu,2 Kazutoshi Mori,3 Tetsuro Fujita,4 Toshisuke Kawasaki,1 and Yasunori Kozutsumi2,*

Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences,1 Laboratory of Molecular Neurobiology,3 and Laboratory of Membrane Biochemistry and Biophysics,2 Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, and Department of Pharmaceutical Manufacturing Chemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101,4 Japan

Received 28 December 1999/Returned for modification 31 January 2000/Accepted 13 March 2000

ISP-1 is a new type of immunosuppressant, the structure of which is homologous to that of sphingosine. In a previous study, ISP-1 was found to inhibit mammalian serine palmitoyltransferase, the primary enzyme involved in sphingolipid biosynthesis, and to reduce the intracellular pool of sphingolipids. ISP-1 induces the apoptosis of cytotoxic T cells, which is triggered by decreases in the intracellular levels of sphingolipids. In this study, the inhibition of yeast (Saccharomyces cerevisiae) proliferation by ISP-1 was observed. This ISP-1-induced growth inhibition was also triggered by decreases in the intracellular levels of sphingolipids. In addition, DNA duplication without cytokinesis was detected in ISP-1-treated yeast cells on flow cytometry analysis. We have cloned multicopy suppressor genes of yeast which overcome the lethal sphingolipid depletion induced by ISP-1. One of these genes, SLI2, is synonymous with YPK1, which encodes a serine/threonine kinase. Kinase-dead mutants of YPK1 did not show any resistance to ISP-1, leading us to predict that the kinase activity of the Ypk1 protein should be essential for this resistance to ISP-1. Ypk1 protein overexpression had no effect on sphingolipid biosynthesis by the yeast. Furthermore, both the phosphorylation and intracellular localization of the Ypk1 protein were regulated by the intracellular sphingolipid levels. These data suggest that the Ypk1 protein is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. The Ypk1 protein was reported to be a functional homologue of the mammalian protein kinase SGK, which is a downstream kinase of 3-phosphoinositide-dependent kinase 1 (PDK1). PDK1 phosphotidylinositol (PI) is regulated by PI-3,4,5-triphosphate and PI-3,4-bisphosphate through the pleckstrin homology (PH) domain. Overexpression of mammalian SGK also overcomes the sphingolipid depletion in yeast. Taking both the inability to produce PI-3,4,5-triphosphate and PI-3,4-bisphosphate and the lack of a PH domain in the yeast homologue of PDK1, the Pkh1 protein, into account, these findings further suggest that yeast may use sphingolipids instead of inositol phospholipids as lipid mediators.

* Corresponding author. Mailing address: Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida-shimoadachi, Kyoto 606-8501, Japan. Phone: 81-75-753-4562. Fax: 81-75-753-4605. E-mail: yasu{at}pharm.kyoto-u.ac.jp.

Molecular and Cellular Biology, June 2000, p. 4411-4419, Vol. 20, No. 12
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Frohlich, F., Moreira, K., Aguilar, P. S., Hubner, N. C., Mann, M., Walter, P., Walther, T. C. (2009). A genome-wide screen for genes affecting eisosomes reveals Nce102 function in sphingolipid signaling. JCB 185: 1227-1242 [Abstract] [Full Text]  
  • Berchtold, D., Walther, T. C. (2009). TORC2 Plasma Membrane Localization Is Essential for Cell Viability and Restricted to a Distinct Domain. Mol. Biol. Cell 20: 1565-1575 [Abstract] [Full Text]  
  • Dickson, R. C. (2008). Thematic Review Series: Sphingolipids. New insights into sphingolipid metabolism and function in budding yeast. J. Lipid Res. 49: 909-921 [Abstract] [Full Text]  
  • Jin, H., McCaffery, J. M., Grote, E. (2008). Ergosterol promotes pheromone signaling and plasma membrane fusion in mating yeast. JCB 180: 813-826 [Abstract] [Full Text]  
  • Sonda, S., Stefanic, S., Hehl, A. B. (2008). A Sphingolipid Inhibitor Induces a Cytokinesis Arrest and Blocks Stage Differentiation in Giardia lamblia. Antimicrob. Agents Chemother. 52: 563-569 [Abstract] [Full Text]  
  • Daquinag, A., Fadri, M., Jung, S. Y., Qin, J., Kunz, J. (2007). The Yeast PH Domain Proteins Slm1 and Slm2 Are Targets of Sphingolipid Signaling during the Response to Heat Stress. Mol. Cell. Biol. 27: 633-650 [Abstract] [Full Text]  
  • Brace, J. L., Lester, R. L., Dickson, R. C., Rudin, C. M. (2007). SVF1 Regulates Cell Survival by Affecting Sphingolipid Metabolism in Saccharomyces cerevisiae. Genetics 175: 65-76 [Abstract] [Full Text]  
  • Sobko, A. (2006). Systems Biology of AGC Kinases in Fungi. Sci Signal 2006: re9-re9 [Abstract] [Full Text]  
  • Bultynck, G., Heath, V. L., Majeed, A. P., Galan, J.-M., Haguenauer-Tsapis, R., Cyert, M. S. (2006). Slm1 and Slm2 Are Novel Substrates of the Calcineurin Phosphatase Required for Heat Stress-Induced Endocytosis of the Yeast Uracil Permease. Mol. Cell. Biol. 26: 4729-4745 [Abstract] [Full Text]  
  • Grosshans, B. L., Grotsch, H., Mukhopadhyay, D., Fernandez, I. M., Pfannstiel, J., Idrissi, F.-Z., Lechner, J., Riezman, H., Geli, M. I. (2006). TEDS Site Phosphorylation of the Yeast Myosins I Is Required for Ligand-induced but Not for Constitutive Endocytosis of the G Protein-coupled Receptor Ste2p. J. Biol. Chem. 281: 11104-11114 [Abstract] [Full Text]  
  • Meier, K. D., Deloche, O., Kajiwara, K., Funato, K., Riezman, H. (2006). Sphingoid Base Is Required for Translation Initiation during Heat Stress in Saccharomyces cerevisiae. Mol. Biol. Cell 17: 1164-1175 [Abstract] [Full Text]  
  • Kamada, Y., Fujioka, Y., Suzuki, N. N., Inagaki, F., Wullschleger, S., Loewith, R., Hall, M. N., Ohsumi, Y. (2005). Tor2 Directly Phosphorylates the AGC Kinase Ypk2 To Regulate Actin Polarization. Mol. Cell. Biol. 25: 7239-7248 [Abstract] [Full Text]  
  • Bimbo, A., Liu, J., Balasubramanian, M. K. (2005). Roles of Pdk1p, a Fission Yeast Protein Related to Phosphoinositide-dependent Protein Kinase, in the Regulation of Mitosis and Cytokinesis. Mol. Biol. Cell 16: 3162-3175 [Abstract] [Full Text]  
  • Liu, K., Zhang, X., Lester, R. L., Dickson, R. C. (2005). The Sphingoid Long Chain Base Phytosphingosine Activates AGC-type Protein Kinases in Saccharomyces cerevisiae Including Ypk1, Ypk2, and Sch9. J. Biol. Chem. 280: 22679-22687 [Abstract] [Full Text]  
  • Levin, D. E. (2005). Cell Wall Integrity Signaling in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 69: 262-291 [Abstract] [Full Text]  
  • Kobayashi, T., Takematsu, H., Yamaji, T., Hiramoto, S., Kozutsumi, Y. (2005). Disturbance of Sphingolipid Biosynthesis Abrogates the Signaling of Mss4, Phosphatidylinositol-4-phosphate 5-Kinase, in Yeast. J. Biol. Chem. 280: 18087-18094 [Abstract] [Full Text]  
  • Roelants, F. M., Torrance, P. D., Thorner, J. (2004). Differential roles of PDK1- and PDK2-phosphorylation sites in the yeast AGC kinases Ypk1, Pkc1 and Sch9. Microbiology 150: 3289-3304 [Abstract] [Full Text]  
  • Zhang, X., Lester, R. L., Dickson, R. C. (2004). Pil1p and Lsp1p Negatively Regulate the 3-Phosphoinositide-dependent Protein Kinase-like Kinase Pkh1p and Downstream Signaling Pathways Pkc1p and Ypk1p. J. Biol. Chem. 279: 22030-22038 [Abstract] [Full Text]  
  • Maiyar, A. C., Leong, M. L.L., Firestone, G. L. (2003). Importin-alpha Mediates the Regulated Nuclear Targeting of Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by Recognition of a Nuclear Localization Signal in the Kinase Central Domain. Mol. Biol. Cell 14: 1221-1239 [Abstract] [Full Text]  
  • Hearn, J. D., Lester, R. L., Dickson, R. C. (2003). The Uracil Transporter Fur4p Associates with Lipid Rafts. J. Biol. Chem. 278: 3679-3686 [Abstract] [Full Text]  
  • Kamynina, E., Staub, O. (2002). Concerted action of ENaC, Nedd4-2, and Sgk1 in transepithelial Na+ transport. Am. J. Physiol. Renal Physiol. 283: F377-F387 [Abstract] [Full Text]  
  • Roelants, F. M., Torrance, P. D., Bezman, N., Thorner, J. (2002). Pkh1 and Pkh2 Differentially Phosphorylate and Activate Ypk1 and Ykr2 and Define Protein Kinase Modules Required for Maintenance of Cell Wall Integrity. Mol. Biol. Cell 13: 3005-3028 [Abstract] [Full Text]  
  • Gelperin, D., Horton, L., DeChant, A., Hensold, J., Lemmon, S. K. (2002). Loss of Ypk1 Function Causes Rapamycin Sensitivity, Inhibition of Translation Initiation and Synthetic Lethality in 14-3-3-Deficient Yeast. Genetics 161: 1453-1464 [Abstract] [Full Text]  
  • Schmelzle, T., Helliwell, S. B., Hall, M. N. (2002). Yeast Protein Kinases and the RHO1 Exchange Factor TUS1 Are Novel Components of the Cell Integrity Pathway in Yeast. Mol. Cell. Biol. 22: 1329-1339 [Abstract] [Full Text]  
  • Hla, T., Lee, M.-J., Ancellin, N., Paik, J. H., Kluk, M. J. (2001). Lysophospholipids--Receptor Revelations. Science 294: 1875-1878 [Abstract] [Full Text]  
  • Lang, F., Cohen, P. (2001). Regulation and Physiological Roles of Serum- and Glucocorticoid-Induced Protein Kinase Isoforms. Sci Signal 2001: re17-re17 [Abstract] [Full Text]  
  • deHart, A. K.A., Schnell, J. D., Allen, D. A., Hicke, L. (2002). The conserved Pkh-Ypk kinase cascade is required for endocytosis in yeast. JCB 156: 241-248 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»