An Essential Function of a Phosphoinositide-Specific Phospholipase C Is Relieved by Inhibition of a Cyclin-Dependent Protein Kinase in the Yeast Saccharomyces cerevisiae

Corresponding author: Jeffrey S. Flick, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, flickjs{at}ctrvax.vanderbilt.edu (E-mail).

Communicating editor: M. JOHNSTON

The PLC1 gene product of Saccharomyces cerevisiae is a homolog of the isoform of mammalian phosphoinositide-specific phospholipase C (PI-PLC). We found that two genes (SPL1 and SPL2), when overexpressed, can bypass the temperature-sensitive growth defect of a plc1 cell. SPL1 is identical to the PHO81 gene, which encodes an inhibitor of a cyclin (Pho80p)-dependent protein kinase (Pho85p) complex (Cdk). In addition to overproduction of Pho81p, two other conditions that inactivate this Cdk, a cyclin (pho80) mutation and growth on low-phosphate medium, also permitted growth of plc1 cells at the restrictive temperature. Suppression of the temperature sensitivity of plc1 cells by pho80 does not depend upon the Pho4p transcriptional regulator, the only known substrate of the Pho80p/Pho85p Cdk. The second suppressor, SPL2, encodes a small (17-kD) protein that bears similarity to the ankyrin repeat regions present in Pho81p and in other known Cdk inhibitors. Both pho81 and spl2 show a synthetic phenotype in combination with plc1. Unlike single mutants, plc1 pho81 and plc1 spl2 double mutants were unable to grow on synthetic complete medium, but were able to grow on rich medium.

This article has been cited by other articles:

				J. D. Stallings, Y. X. Zeng, F. Narvaez, and M. J. Rebecchi Phospholipase C-{delta}1 Expression Is Linked to Proliferation, DNA Synthesis, and Cyclin E Levels J. Biol. Chem., May 16, 2008; 283(20): 13992 - 14001. [Abstract] [Full Text] [PDF]

				W. Fei, G. Alfaro, B.-P. Muthusamy, Z. Klaassen, T. R. Graham, H. Yang, and C. T. Beh Genome-Wide Analysis of Sterol-Lipid Storage and Trafficking in Saccharomyces cerevisiae Eukaryot. Cell, February 1, 2008; 7(2): 401 - 414. [Abstract] [Full Text] [PDF]

				Y.-S. Lee, S. Mulugu, J. D. York, and E. K. O'Shea Regulation of a Cyclin-CDK-CDK Inhibitor Complex by Inositol Pyrophosphates Science, April 6, 2007; 316(5821): 109 - 112. [Abstract] [Full Text] [PDF]

				S. L. Tai, V. M. Boer, P. Daran-Lapujade, M. C. Walsh, J. H. de Winde, J.-M. Daran, and J. T. Pronk Two-dimensional Transcriptome Analysis in Chemostat Cultures: COMBINATORIAL EFFECTS OF OXYGEN AVAILABILITY AND MACRONUTRIENT LIMITATION IN SACCHAROMYCES CEREVISIAE J. Biol. Chem., January 7, 2005; 280(1): 437 - 447. [Abstract] [Full Text] [PDF]

				N. M. Perera, R. H. Michell, and S. K. Dove Hypo-osmotic Stress Activates Plc1p-dependent Phosphatidylinositol 4,5-Bisphosphate Hydrolysis and Inositol Hexakisphosphate Accumulation in Yeast J. Biol. Chem., February 13, 2004; 279(7): 5216 - 5226. [Abstract] [Full Text] [PDF]

				J. W. Verbsky, M. P. Wilson, M. V. Kisseleva, P. W. Majerus, and S. R. Wente The Synthesis of Inositol Hexakisphosphate. CHARACTERIZATION OF HUMAN INOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE 2-KINASE J. Biol. Chem., August 23, 2002; 277(35): 31857 - 31862. [Abstract] [Full Text] [PDF]

				S. Huang, D. A. Jeffery, M. D. Anthony, and E. K. O'Shea Functional Analysis of the Cyclin-Dependent Kinase Inhibitor Pho81 Identifies a Novel Inhibitory Domain Mol. Cell. Biol., October 1, 2001; 21(19): 6695 - 6705. [Abstract] [Full Text] [PDF]

				N. Ogawa, J. DeRisi, and P. O. Brown New Components of a System for Phosphate Accumulation and Polyphosphate Metabolism in Saccharomyces cerevisiae Revealed by Genomic Expression Analysis Mol. Biol. Cell, December 1, 2000; 11(12): 4309 - 4321. [Abstract] [Full Text]

				M. J. Rebecchi and S. N. Pentyala Structure, Function, and Control of Phosphoinositide-Specific Phospholipase C Physiol Rev, October 1, 2000; 80(4): 1291 - 1335. [Abstract] [Full Text] [PDF]

				H. Lin, J. H. Choi, J. Hasek, N. DeLillo, W. Lou, and A. Vancura Phospholipase C Is Involved in Kinetochore Function in Saccharomyces cerevisiae Mol. Cell. Biol., May 15, 2000; 20(10): 3597 - 3607. [Abstract] [Full Text]

				M. Nishizawa, Y. Kanaya, and A. Toh-e Mouse Cyclin-dependent Kinase (Cdk) 5 Is a Functional Homologue of a Yeast Cdk, Pho85 Kinase J. Biol. Chem., November 26, 1999; 274(48): 33859 - 33862. [Abstract] [Full Text] [PDF]

				K. Ansari, S. Martin, M. Farkasovsky, I.-M. Ehbrecht, and H. Kuntzel Phospholipase C Binds to the Receptor-like GPR1 Protein and Controls Pseudohyphal Differentiation in Saccharomyces cerevisiae J. Biol. Chem., October 15, 1999; 274(42): 30052 - 30058. [Abstract] [Full Text] [PDF]

				C. M. Alarcon, J. Heitman, and M. E. Cardenas Protein Kinase Activity and Identification of a Toxic Effector Domain of the Target of Rapamycin TOR Proteins in Yeast Mol. Biol. Cell, August 1, 1999; 10(8): 2531 - 2546. [Abstract] [Full Text]

				I. Iraqui, S. Vissers, B. Andre, and A. Urrestarazu Transcriptional Induction by Aromatic Amino Acids in Saccharomyces cerevisiae Mol. Cell. Biol., May 1, 1999; 19(5): 3360 - 3371. [Abstract] [Full Text] [PDF]