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 Huang, D.
Right arrow Articles by Andrews, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huang, D.
Right arrow Articles by Andrews, B.

 Previous Article  |  Next Article 

Mol Cell Biol, June 1998, p. 3289-3299, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Cyclin Partners Determine Pho85 Protein Kinase Substrate Specificity In Vitro and In Vivo: Control of Glycogen Biosynthesis by Pcl8 and Pcl10

Dongqing Huang,1,dagger Jason Moffat,2 Wayne A. Wilson,1 Lynda Moore,2 Christine Cheng,1 Peter J. Roach,1,* and Brenda Andrews2

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5122,1 and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Canada2

Received 7 January 1998/Returned for modification 16 February 1998/Accepted 18 March 1998

In Saccharomyces cerevisiae, PHO85 encodes a cyclin-dependent protein kinase (Cdk) with multiple roles in cell cycle and metabolic controls. In association with the cyclin Pho80, Pho85 controls acid phosphatase gene expression through phosphorylation of the transcription factor Pho4. Pho85 has also been implicated as a kinase that phosphorylates and negatively regulates glycogen synthase (Gsy2), and deletion of PHO85 causes glycogen overaccumulation. We report that the Pcl8/Pcl10 subgroup of cyclins directs Pho85 to phosphorylate glycogen synthase both in vivo and in vitro. Disruption of PCL8 and PCL10 caused hyperaccumulation of glycogen, activation of glycogen synthase, and a reduction in glycogen synthase kinase activity in vivo. However, unlike pho85 mutants, pcl8 pcl10 cells had normal morphologies, grew on glycerol, and showed proper regulation of acid phosphatase gene expression. In vitro, Pho80-Pho85 complexes effectively phosphorylated Pho4 but had much lower activity toward Gsy2. In contrast, Pcl10-Pho85 complexes phosphorylated Gsy2 at Ser-654 and Thr-667, two physiologically relevant sites, but only poorly phosphorylated Pho4. Thus, both the in vitro and in vivo substrate specificity of Pho85 is determined by the cyclin partner. Mutation of PHO85 suppressed the glycogen storage deficiency of snf1 or glc7-1 mutants in which glycogen synthase is locked in an inactive state. Deletion of PCL8 and PCL10 corrected the deficit in glycogen synthase activity in both the snf1 and glc7-1 mutants, but glycogen synthesis was restored only in the glc7-1 mutant strain. This genetic result suggests an additional role for Pho85 in the negative regulation of glycogen accumulation that is independent of Pcl8 and Pcl10.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202-5122. Phone: (317) 274-1582. Fax: (317) 274-4686. E-mail: proach{at}iupvi.edu.

dagger Present address: Department of Molecular and Medical Genetics, University of Toronto, Toronto, Canada.

Mol Cell Biol, June 1998, p. 3289-3299, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Streckfuss-Bomeke, K., Schulze, F., Herzog, B., Scholz, E., Braus, G. H. (2009). Degradation of Saccharomyces cerevisiae Transcription Factor Gcn4 Requires a C-Terminal Nuclear Localization Signal in the Cyclin Pcl5. Eukaryot Cell 8: 496-510 [Abstract] [Full Text]  
  • Aviram, S., Simon, E., Gildor, T., Glaser, F., Kornitzer, D. (2008). Autophosphorylation-Induced Degradation of the Pho85 Cyclin Pcl5 Is Essential for Response to Amino Acid Limitation. Mol. Cell. Biol. 28: 6858-6869 [Abstract] [Full Text]  
  • Rubenstein, E. M., Schmidt, M. C. (2007). Mechanisms Regulating the Protein Kinases of Saccharomyces cerevisiae. Eukaryot Cell 6: 571-583 [Full Text]  
  • Bomeke, K., Pries, R., Korte, V., Scholz, E., Herzog, B., Schulze, F., Braus, G. H. (2006). Yeast Gcn4p Stabilization Is Initiated by the Dissociation of the Nuclear Pho85p/Pcl5p Complex. Mol. Biol. Cell 17: 2952-2962 [Abstract] [Full Text]  
  • Dephoure, N., Howson, R. W., Blethrow, J. D., Shokat, K. M., O'Shea, E. K. (2005). Combining chemical genetics and proteomics to identify protein kinase substrates. Proc. Natl. Acad. Sci. USA 102: 17940-17945 [Abstract] [Full Text]  
  • Gildor, T., Shemer, R., Atir-Lande, A., Kornitzer, D. (2005). Coevolution of Cyclin Pcl5 and Its Substrate Gcn4. Eukaryot Cell 4: 310-318 [Abstract] [Full Text]  
  • Wu, D., Dou, X., Hashmi, S. B., Osmani, S. A. (2004). The Pho80-like Cyclin of Aspergillus nidulans Regulates Development Independently of Its Role in Phosphate Acquisition. J. Biol. Chem. 279: 37693-37703 [Abstract] [Full Text]  
  • Pederson, B. A., Wilson, W. A., Roach, P. J. (2004). Glycogen Synthase Sensitivity to Glucose-6-P Is Important for Controlling Glycogen Accumulation in Saccharomyces cerevisiae. J. Biol. Chem. 279: 13764-13768 [Abstract] [Full Text]  
  • Keniry, M. E., Kemp, H. A., Rivers, D. M., Sprague, G. F. Jr. (2004). The Identification of Pcl1-Interacting Proteins That Genetically Interact With Cla4 May Indicate a Link Between G1 Progression and Mitotic Exit. Genetics 166: 1177-1186 [Abstract] [Full Text]  
  • Tan, Y. S. H., Morcos, P. A., Cannon, J. F. (2003). Pho85 Phosphorylates the Glc7 Protein Phosphatase Regulator Glc8 in Vivo. J. Biol. Chem. 278: 147-153 [Abstract] [Full Text]  
  • Chang, J. S., Henry, K., Wolf, B. L., Geli, M., Lemmon, S. K. (2002). Protein Phosphatase-1 Binding to Scd5p Is Important for Regulation of Actin Organization and Endocytosis in Yeast. J. Biol. Chem. 277: 48002-48008 [Abstract] [Full Text]  
  • Shemer, R., Meimoun, A., Holtzman, T., Kornitzer, D. (2002). Regulation of the Transcription Factor Gcn4 by Pho85 Cyclin Pcl5. Mol. Cell. Biol. 22: 5395-5404 [Abstract] [Full Text]  
  • Huang, D., Moffat, J., Andrews, B. (2002). Dissection of a Complex Phenotype by Functional Genomics Reveals Roles for the Yeast Cyclin-Dependent Protein Kinase Pho85 in Stress Adaptation and Cell Integrity. Mol. Cell. Biol. 22: 5076-5088 [Abstract] [Full Text]  
  • Leng, X., Noble, M., Adams, P. D., Qin, J., Harper, J. W. (2002). Reversal of Growth Suppression by p107 via Direct Phosphorylation by Cyclin D1/Cyclin-Dependent Kinase 4. Mol. Cell. Biol. 22: 2242-2254 [Abstract] [Full Text]  
  • Williams-Hart, T., Wu, X., Tatchell, K. (2002). Protein Phosphatase Type 1 Regulates Ion Homeostasis in Saccharomyces cerevisiae. Genetics 160: 1423-1437 [Abstract] [Full Text]  
  • Wilson, W. A., Wang, Z., Roach, P. J. (2002). Systematic Identification of the Genes Affecting Glycogen Storage in the Yeast Saccharomyces cerevisiae: Implication of the Vacuole as a Determinant of Glycogen Level. Mol. Cell. Proteomics 1: 232-242 [Abstract] [Full Text]  
  • Rutherford, J. C., Jaron, S., Ray, E., Brown, P. O., Winge, D. R. (2001). A second iron-regulatory system in yeast independent of Aft1p. Proc. Natl. Acad. Sci. USA 98: 14322-14327 [Abstract] [Full Text]  
  • Carroll, A. S., Bishop, A. C., DeRisi, J. L., Shokat, K. M., O'Shea, E. K. (2001). Chemical inhibition of the Pho85 cyclin-dependent kinase reveals a role in the environmental stress response. Proc. Natl. Acad. Sci. USA 98: 12578-12583 [Abstract] [Full Text]  
  • Wang, Z., Wilson, W. A., Fujino, M. A., Roach, P. J. (2001). Antagonistic Controls of Autophagy and Glycogen Accumulation by Snf1p, the Yeast Homolog of AMP-Activated Protein Kinase, and the Cyclin-Dependent Kinase Pho85p. Mol. Cell. Biol. 21: 5742-5752 [Abstract] [Full Text]  
  • Anderson, C., Tatchell, K. (2001). Hyperactive Glycogen Synthase Mutants of Saccharomyces cerevisiae Suppress the glc7-1 Protein Phosphatase Mutant. J. Bacteriol. 183: 821-829 [Abstract] [Full Text]  
  • Ren, B., Robert, F., Wyrick, J. J., Aparicio, O., Jennings, E. G., Simon, I., Zeitlinger, J., Schreiber, J., Hannett, N., Kanin, E., Volkert, T. L., Wilson, C. J., Bell, S. P., Young, R. A. (2000). Genome-Wide Location and Function of DNA Binding Proteins. Science 290: 2306-2309 [Abstract] [Full Text]  
  • Gasch, A. P., Spellman, P. T., Kao, C. M., Carmel-Harel, O., Eisen, M. B., Storz, G., Botstein, D., Brown, P. O. (2000). Genomic Expression Programs in the Response of Yeast Cells to Environmental Changes. Mol. Biol. Cell 11: 4241-4257 [Abstract] [Full Text]  
  • Pawson, T., Nash, P. (2000). Protein-protein interactions define specificity in signal transduction. Genes Dev. 14: 1027-1047 [Full Text]  
  • Le Roch, K., Sestier, C., Dorin, D., Waters, N., Kappes, B., Chakrabarti, D., Meijer, L., Doerig, C. (2000). Activation of a Plasmodium falciparum cdc2-related Kinase by Heterologous p25 and Cyclin H. FUNCTIONAL CHARACTERIZATION OF A P. FALCIPARUM CYCLIN HOMOLOGUE. J. Biol. Chem. 275: 8952-8958 [Abstract] [Full Text]  
  • Meimoun, A., Holtzman, T., Weissman, Z., McBride, H. J., Stillman, D. J., Fink, G. R., Kornitzer, D. (2000). Degradation of the Transcription Factor Gcn4 Requires the Kinase Pho85 and the SCFCDC4 Ubiquitin-Ligase Complex. Mol. Biol. Cell 11: 915-927 [Abstract] [Full Text]  
  • Huang, D., Patrick, G., Moffat, J., Tsai, L.-H., Andrews, B. (1999). Mammalian Cdk5 is a functional homologue of the budding yeast Pho85 cyclin-dependent protein kinase. Proc. Natl. Acad. Sci. USA 96: 14445-14450 [Abstract] [Full Text]  
  • Nishizawa, M., Kanaya, Y., Toh-e, A. (1999). Mouse Cyclin-dependent Kinase (Cdk) 5 Is a Functional Homologue of a Yeast Cdk, Pho85 Kinase. J. Biol. Chem. 274: 33859-33862 [Abstract] [Full Text]  
  • Wilson, W. A., Mahrenholz, A. M., Roach, P. J. (1999). Substrate Targeting of the Yeast Cyclin-Dependent Kinase Pho85p by the Cyclin Pcl10p. Mol. Cell. Biol. 19: 7020-7030 [Abstract] [Full Text]  
  • Colwill, K., Field, D., Moore, L., Friesen, J., Andrews, B. (1999). In Vivo Analysis of the Domains of Yeast Rvs167p Suggests Rvs167p Function Is Mediated Through Multiple Protein Interactions. Genetics 152: 881-893 [Abstract] [Full Text]  
  • Silljé, H. H. W., Paalman, J. W. G., ter Schure, E. G., Olsthoorn, S. Q. B., Verkleij, A. J., Boonstra, J., Verrips, C. T. (1999). Function of Trehalose and Glycogen in Cell Cycle Progression and Cell Viability in Saccharomyces cerevisiae. J. Bacteriol. 181: 396-400 [Abstract] [Full Text]  
  • Mendenhall, M. D., Hodge, A. E. (1998). Regulation of Cdc28 Cyclin-Dependent Protein Kinase Activity during the Cell Cycle of the Yeast Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 62: 1191-1243 [Abstract] [Full Text]  
  • Yang, R., Chun, K. T., Wek, R. C. (1998). Mitochondrial Respiratory Mutants in Yeast Inhibit Glycogen Accumulation by Blocking Activation of Glycogen Synthase. J. Biol. Chem. 273: 31337-31344 [Abstract] [Full Text]  
  • Espinoza, F. H., Farrell, A., Nourse, J. L., Chamberlin, H. M., Gileadi, O., Morgan, D. O. (1998). Cak1 Is Required for Kin28 Phosphorylation and Activation In Vivo. Mol. Cell. Biol. 18: 6365-6373 [Abstract] [Full Text]  
  • Pederson, B. A., Cheng, C., Wilson, W. A., Roach, P. J. (2000). Regulation of Glycogen Synthase. IDENTIFICATION OF RESIDUES INVOLVED IN REGULATION BY THE ALLOSTERIC LIGAND GLUCOSE-6-P AND BY PHOSPHORYLATION. J. Biol. Chem. 275: 27753-27761 [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»