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 Shulewitz, M. J.
Right arrow Articles by Thorner, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shulewitz, M. J.
Right arrow Articles by Thorner, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 1999, p. 7123-7137, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Hsl7 Localizes to a Septin Ring and Serves as an Adapter in a Regulatory Pathway That Relieves Tyrosine Phosphorylation of Cdc28 Protein Kinase in Saccharomyces cerevisiae

Mark J. Shulewitz, Carla J. Inouye,dagger and Jeremy Thorner*

Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, California 94720-3202

Received 25 March 1999/Returned for modification 13 May 1999/Accepted 22 June 1999

Successful mitosis requires faithful DNA replication, spindle assembly, chromosome segregation, and cell division. In the budding yeast Saccharomyces cerevisiae, the G2-to-M transition requires activation of Clb-bound forms of the protein kinase, Cdc28. These complexes are held in an inactive state via phosphorylation of Tyr19 in the ATP-binding loop of Cdc28 by the Swe1 protein kinase. The HSL1 and HSL7 gene products act as negative regulators of Swe1. Hsl1 is a large (1,518-residue) protein kinase with an N-terminal catalytic domain and a very long C-terminal extension. Hsl1 localizes to the incipient site of cytokinesis in the bud neck in a septin-dependent manner; however, the function of Hsl7 was not previously known. Using both indirect immunofluorescence with anti-Hsl7 antibodies and a fusion of Hsl7 to green fluorescent protein, we found that Hsl7 also localizes to the bud neck, congruent with the septin ring that faces the daughter cell. Both Swe1 and a segment of the C terminus of Hsl1 (which has no sequence counterpart in two Hsl1-related protein kinases, Gin4 and Kcc4) were identified as gene products that interact with Hsl7 in a two-hybrid screen of a random S. cerevisiae cDNA library. Hsl7 plus Swe1 and Hsl7 plus Hsl1 can be coimmunoprecipitated from extracts of cells overexpressing these proteins, confirming that Hsl7 physically associates with both partners. Also consistent with the two-hybrid results, Hsl7 coimmunoprecipitates with full-length Hsl1 less efficiently than with a C-terminal fragment of Hsl1. Moreover, Hsl7 does not localize to the bud neck in an hsl1Delta mutant, whereas Hsl1 is localized normally in an hsl7Delta mutant. Phosphorylation and ubiquitinylation of Swe1, preludes to its destruction, are severely reduced in cells lacking either Hsl1 or Hsl7 (or both), as judged by an electrophoretic mobility shift assay. Collectively, these data suggest that formation of the septin rings provides sites for docking Hsl1, exposing its C terminus and thereby permitting recruitment of Hsl7. Hsl7, in turn, presents its cargo of bound Swe1, allowing phosphorylation by Hsl1. Thus, Hsl1 and Hsl7 promote proper timing of cell cycle progression by coupling septin ring assembly to alleviation of Swe1-dependent inhibition of Cdc28. Furthermore, like septins and Hsl1, homologs of Hsl7 are found in fission yeast, flies, worms, and humans, suggesting that its function in this control mechanism may be conserved in all eukaryotes.

* Corresponding author. Mailing address: Department of Molecular and Cell Biology, Room 401, Barker Hall, Corner of Hearst and Oxford St., Berkeley, CA 94720-3202. Phone: (510) 642-2558. Fax: (510) 643-5035. E-mail: jeremy{at}socrates.berkeley.edu.

dagger Present address: Tjian Laboratory, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720-3204.

Molecular and Cellular Biology, October 1999, p. 7123-7137, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Liang, F., Jin, F., Liu, H., Wang, Y. (2009). The Molecular Function of the Yeast Polo-like Kinase Cdc5 in Cdc14 Release during Early Anaphase. Mol. Biol. Cell 20: 3671-3679 [Abstract] [Full Text]  
  • Crutchley, J., King, K. M., Keaton, M. A., Szkotnicki, L., Orlando, D. A., Zyla, T. R., Bardes, E. S.G., Lew, D. J. (2009). Molecular Dissection of the Checkpoint Kinase Hsl1p. Mol. Biol. Cell 20: 1926-1936 [Abstract] [Full Text]  
  • Szkotnicki, L., Crutchley, J. M., Zyla, T. R., Bardes, E. S.G., Lew, D. J. (2008). The Checkpoint Kinase Hsl1p Is Activated by Elm1p-dependent Phosphorylation. Mol. Biol. Cell 19: 4675-4686 [Abstract] [Full Text]  
  • Keaton, M. A., Szkotnicki, L., Marquitz, A. R., Harrison, J., Zyla, T. R., Lew, D. J. (2008). Nucleocytoplasmic Trafficking of G2/M Regulators in Yeast. Mol. Biol. Cell 19: 4006-4018 [Abstract] [Full Text]  
  • Gomez, E. B., Nugent, R. L., Laria, S., Forsburg, S. L. (2008). Schizosaccharomyces pombe Histone Acetyltransferase Mst1 (KAT5) Is an Essential Protein Required for Damage Response and Chromosome Segregation. Genetics 179: 757-771 [Abstract] [Full Text]  
  • Ko, N., Nishihama, R., Tully, G. H., Ostapenko, D., Solomon, M. J., Morgan, D. O., Pringle, J. R. (2007). Identification of Yeast IQGAP (Iqg1p) as an Anaphase-Promoting-Complex Substrate and Its Role in Actomyosin-Ring-Independent Cytokinesis. Mol. Biol. Cell 18: 5139-5153 [Abstract] [Full Text]  
  • Loewen, C. J.R., Young, B. P., Tavassoli, S., Levine, T. P. (2007). Inheritance of cortical ER in yeast is required for normal septin organization. JCB 179: 467-483 [Abstract] [Full Text]  
  • Bachand, F. (2007). Protein Arginine Methyltransferases: from Unicellular Eukaryotes to Humans. Eukaryot Cell 6: 889-898 [Full Text]  
  • Rubenstein, E. M., Schmidt, M. C. (2007). Mechanisms Regulating the Protein Kinases of Saccharomyces cerevisiae. Eukaryot Cell 6: 571-583 [Full Text]  
  • Park, H.-O., Bi, E. (2007). Central Roles of Small GTPases in the Development of Cell Polarity in Yeast and Beyond. Microbiol. Mol. Biol. Rev. 71: 48-96 [Abstract] [Full Text]  
  • Rodriguez-Escudero, I., Rotger, R., Cid, V. J., Molina, M. (2006). Inhibition of Cdc42-dependent signalling in Saccharomyces cerevisiae by phosphatase-dead SigD/SopB from Salmonella typhimurium.. Microbiology 152: 3437-3452 [Abstract] [Full Text]  
  • Ruault, M., Pillus, L. (2006). Chromatin-Modifiying Enzymes Are Essential When the Saccharomyces cerevisiae Morphogenesis Checkpoint Is Constitutively Activated. Genetics 174: 1135-1149 [Abstract] [Full Text]  
  • Helfer, H., Gladfelter, A. S. (2006). AgSwe1p Regulates Mitosis in Response to Morphogenesis and Nutrients in Multinucleated Ashbya gossypii Cells. Mol. Biol. Cell 17: 4494-4512 [Abstract] [Full Text]  
  • Asano, S., Park, J.-E., Yu, L.-R., Zhou, M., Sakchaisri, K., Park, C. J., Kang, Y. H., Thorner, J., Veenstra, T. D., Lee, K. S. (2006). Direct Phosphorylation and Activation of a Nim1-related Kinase Gin4 by Elm1 in Budding Yeast. J. Biol. Chem. 281: 27090-27098 [Abstract] [Full Text]  
  • Calonge, T. M., O'Connell, M. J. (2006). Antagonism of Chk1 Signaling in the G2 DNA Damage Checkpoint by Dominant Alleles of Cdr1. Genetics 174: 113-123 [Abstract] [Full Text]  
  • Jiang, Y. (2006). Regulation of the Cell Cycle by Protein Phosphatase 2A in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 70: 440-449 [Abstract] [Full Text]  
  • Liu, H., Wang, Y. (2006). The Function and Regulation of Budding Yeast Swe1 in Response to Interrupted DNA Synthesis. Mol. Biol. Cell 17: 2746-2756 [Abstract] [Full Text]  
  • Truckses, D. M., Bloomekatz, J. E., Thorner, J. (2006). The RA Domain of Ste50 Adaptor Protein Is Required for Delivery of Ste11 to the Plasma Membrane in the Filamentous Growth Signaling Pathway of the Yeast Saccharomyces cerevisiae. Mol. Cell. Biol. 26: 912-928 [Abstract] [Full Text]  
  • Strahl, T., Hama, H., DeWald, D. B., Thorner, J. (2005). Yeast phosphatidylinositol 4-kinase, Pik1, has essential roles at the Golgi and in the nucleus. JCB 171: 967-979 [Abstract] [Full Text]  
  • Douglas, L. M., Alvarez, F. J., McCreary, C., Konopka, J. B. (2005). Septin Function in Yeast Model Systems and Pathogenic Fungi. Eukaryot Cell 4: 1503-1512 [Full Text]  
  • Kozubowski, L., Larson, J. R., Tatchell, K. (2005). Role of the Septin Ring in the Asymmetric Localization of Proteins at the Mother-Bud Neck in Saccharomyces cerevisiae. Mol. Biol. Cell 16: 3455-3466 [Abstract] [Full Text]  
  • Luedeke, C., Frei, S. B., Sbalzarini, I., Schwarz, H., Spang, A., Barral, Y. (2005). Septin-dependent compartmentalization of the endoplasmic reticulum during yeast polarized growth. JCB 169: 897-908 [Abstract] [Full Text]  
  • Yamada, A., Duffy, B., Perry, J. A., Kornbluth, S. (2004). DNA replication checkpoint control of Wee1 stability by vertebrate Hsl7. JCB 167: 841-849 [Abstract] [Full Text]  
  • Kadota, J., Yamamoto, T., Yoshiuchi, S., Bi, E., Tanaka, K. (2004). Septin Ring Assembly Requires Concerted Action of Polarisome Components, a PAK Kinase Cla4p, and the Actin Cytoskeleton in Saccharomyces cerevisiae. Mol. Biol. Cell 15: 5329-5345 [Abstract] [Full Text]  
  • Park, J.-E., Park, C. J., Sakchaisri, K., Karpova, T., Asano, S., McNally, J., Sunwoo, Y., Leem, S.-H., Lee, K. S. (2004). Novel Functional Dissection of the Localization-Specific Roles of Budding Yeast Polo Kinase Cdc5p. Mol. Cell. Biol. 24: 9873-9886 [Abstract] [Full Text]  
  • Pruyne, D., Gao, L., Bi, E., Bretscher, A. (2004). Stable and Dynamic Axes of Polarity Use Distinct Formin Isoforms in Budding Yeast. Mol. Biol. Cell 15: 4971-4989 [Abstract] [Full Text]  
  • Morrell, J. L., Nichols, C. B., Gould, K. L. (2004). The GIN4 family kinase, Cdr2p, acts independently of septins in fission yeast. J. Cell Sci. 117: 5293-5302 [Abstract] [Full Text]  
  • Versele, M., Gullbrand, B., Shulewitz, M. J., Cid, V. J., Bahmanyar, S., Chen, R. E., Barth, P., Alber, T., Thorner, J. (2004). Protein-Protein Interactions Governing Septin Heteropentamer Assembly and Septin Filament Organization in Saccharomyces cerevisiae. Mol. Biol. Cell 15: 4568-4583 [Abstract] [Full Text]  
  • Sakchaisri, K., Asano, S., Yu, L.-R., Shulewitz, M. J., Park, C. J., Park, J.-E., Cho, Y.-W., Veenstra, T. D., Thorner, J., Lee, K. S. (2004). Coupling morphogenesis to mitotic entry. Proc. Natl. Acad. Sci. USA 101: 4124-4129 [Abstract] [Full Text]  
  • Versele, M., Thorner, J. (2004). Septin collar formation in budding yeast requires GTP binding and direct phosphorylation by the PAK, Cla4. JCB 164: 701-715 [Abstract] [Full Text]  
  • Kellogg, D. R. (2003). Wee1-dependent mechanisms required for coordination of cell growth and cell division. J. Cell Sci. 116: 4883-4890 [Abstract] [Full Text]  
  • Caviston, J. P., Longtine, M., Pringle, J. R., Bi, E. (2003). The Role of Cdc42p GTPase-activating Proteins in Assembly of the Septin Ring in Yeast. Mol. Biol. Cell 14: 4051-4066 [Abstract] [Full Text]  
  • Sreenivasan, A., Bishop, A. C., Shokat, K. M., Kellogg, D. R. (2003). Specific Inhibition of Elm1 Kinase Activity Reveals Functions Required for Early G1 Events. Mol. Cell. Biol. 23: 6327-6337 [Abstract] [Full Text]  
  • Theesfeld, C. L., Zyla, T. R., Bardes, E. G.S., Lew, D. J. (2003). A Monitor for Bud Emergence in the Yeast Morphogenesis Checkpoint. Mol. Biol. Cell 14: 3280-3291 [Abstract] [Full Text]  
  • Wiley, D. J., Marcus, S., D'urso, G., Verde, F. (2003). Control of Cell Polarity in Fission Yeast by Association of Orb6p Kinase with the Highly Conserved Protein Methyltransferase Skb1p. J. Biol. Chem. 278: 25256-25263 [Abstract] [Full Text]  
  • Kozubowski, L., Panek, H., Rosenthal, A., Bloecher, A., DeMarini, D. J., Tatchell, K. (2003). A Bni4-Glc7 Phosphatase Complex That Recruits Chitin Synthase to the Site of Bud Emergence. Mol. Biol. Cell 14: 26-39 [Abstract] [Full Text]  
  • Cullen, P. J., Sprague, G. F. Jr. (2002). The Glc7p-Interacting Protein Bud14p Attenuates Polarized Growth, Pheromone Response, and Filamentous Growth in Saccharomyces cerevisiae. Eukaryot Cell 1: 884-894 [Abstract] [Full Text]  
  • Lee, P. R., Song, S., Ro, H.-S., Park, C. J., Lippincott, J., Li, R., Pringle, J. R., De Virgilio, C., Longtine, M. S., Lee, K. S. (2002). Bni5p, a Septin-Interacting Protein, Is Required for Normal Septin Function and Cytokinesis in Saccharomyces cerevisiae. Mol. Cell. Biol. 22: 6906-6920 [Abstract] [Full Text]  
  • Gentry, M. S., Hallberg, R. L. (2002). Localization of Saccharomyces cerevisiae Protein Phosphatase 2A Subunits throughout Mitotic Cell Cycle. Mol. Biol. Cell 13: 3477-3492 [Abstract] [Full Text]  
  • McMillan, J. N., Theesfeld, C. L., Harrison, J. C., Bardes, E. S. G., Lew, D. J. (2002). Determinants of Swe1p Degradation in Saccharomyces cerevisiae. Mol. Biol. Cell 13: 3560-3575 [Abstract] [Full Text]  
  • Cid, V. J., Jimenez, J., Molina, M., Sanchez, M., Nombela, C., Thorner, J. W. (2002). Orchestrating the cell cycle in yeast: sequential localization of key mitotic regulators at the spindle pole and the bud neck. Microbiology 148: 2647-2659 [Full Text]  
  • Mortensen, E. M., McDonald, H., Yates, J. III, Kellogg, D. R. (2002). Cell Cycle-dependent Assembly of a Gin4-Septin Complex. Mol. Biol. Cell 13: 2091-2105 [Abstract] [Full Text]  
  • Gale, C., Gerami-Nejad, M., McClellan, M., Vandoninck, S., Longtine, M. S., Berman, J. (2001). Candida albicans Int1p Interacts with the Septin Ring in Yeast and Hyphal Cells. Mol. Biol. Cell 12: 3538-3549 [Abstract] [Full Text]  
  • Burton, J. L., Solomon, M. J. (2001). D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p. Genes Dev. 15: 2381-2395 [Abstract] [Full Text]  
  • Drees, B. L., Sundin, B., Brazeau, E., Caviston, J. P., Chen, G.-C., Guo, W., Kozminski, K. G., Lau, M. W., Moskow, J. J., Tong, A., Schenkman, L. R., McKenzie, A. III, Brennwald, P., Longtine, M., Bi, E., Chan, C., Novick, P., Boone, C., Pringle, J. R., Davis, T. N., Fields, S., Drubin, D. G. (2001). A protein interaction map for cell polarity development. JCB 154: 549-576 [Abstract] [Full Text]  
  • Bartholomew, C. R., Woo, S. H., Chung, Y. S., Jones, C., Hardy, C. F. J. (2001). Cdc5 Interacts with the Wee1 Kinase in Budding Yeast. Mol. Cell. Biol. 21: 4949-4959 [Abstract] [Full Text]  
  • La Valle, R., Wittenberg, C. (2001). A Role for the Swe1 Checkpoint Kinase During Filamentous Growth of Saccharomyces cerevisiae. Genetics 158: 549-562 [Abstract] [Full Text]  
  • Cid, V. J., Shulewitz, M. J., McDonald, K. L., Thorner, J. (2001). Dynamic Localization of the Swe1 Regulator Hsl7 During the Saccharomyces cerevisiae Cell Cycle. Mol. Biol. Cell 12: 1645-1669 [Abstract] [Full Text]  
  • Momany, M., Zhao, J., Lindsey, R., Westfall, P. J. (2001). Characterization of the Aspergillus nidulans Septin (asp) Gene Family. Genetics 157: 969-977 [Abstract] [Full Text]  
  • Mitchell, D. A., Sprague, G. F. Jr. (2001). The Phosphotyrosyl Phosphatase Activator, Ncs1p (Rrd1p), Functions with Cla4p To Regulate the G2/M Transition in Saccharomyces cerevisiae. Mol. Cell. Biol. 21: 488-500 [Abstract] [Full Text]  
  • Kartmann, B, Roth, D (2001). Novel roles for mammalian septins: from vesicle trafficking to oncogenesis. J. Cell Sci. 114: 839-844 [Abstract]  
  • Zimmerman, Z. A., Kellogg, D. R. (2001). The Sda1 Protein Is Required for Passage through Start. Mol. Biol. Cell 12: 201-219 [Abstract] [Full Text]  
  • Cullen, P. J., Sprague, G. F. Jr. (2000). Glucose depletion causes haploid invasive growth in yeast. Proc. Natl. Acad. Sci. USA 10.1073/pnas.240345197v1 [Abstract] [Full Text]  
  • Yang, H., Jiang, W., Gentry, M., Hallberg, R. L. (2000). Loss of a Protein Phosphatase 2A Regulatory Subunit (Cdc55p) Elicits Improper Regulation of Swe1p Degradation. Mol. Cell. Biol. 20: 8143-8156 [Abstract] [Full Text]  
  • Longtine, M. S., Theesfeld, C. L., McMillan, J. N., Weaver, E., Pringle, J. R., Lew, D. J. (2000). Septin-Dependent Assembly of a Cell Cycle-Regulatory Module in Saccharomyces cerevisiae. Mol. Cell. Biol. 20: 4049-4061 [Abstract] [Full Text]  
  • McMillan, J. N., Longtine, M. S., Sia, R. A. L., Theesfeld, C. L., Bardes, E. S. G., Pringle, J. R., Lew, D. J. (1999). The Morphogenesis Checkpoint in Saccharomyces cerevisiae: Cell Cycle Control of Swe1p Degradation by Hsl1p and Hsl7p. Mol. Cell. Biol. 19: 6929-6939 [Abstract] [Full Text]  
  • Bao, S., Qyang, Y., Yang, P., Kim, H., Du, H., Bartholomeusz, G., Henkel, J., Pimental, R., Verde, F., Marcus, S. (2001). The Highly Conserved Protein Methyltransferase, Skb1, Is a Mediator of Hyperosmotic Stress Response in the Fission Yeast Schizosaccharomyces pombe. J. Biol. Chem. 276: 14549-14552 [Abstract] [Full Text]  
  • Cullen, P. J., Sprague, G. F. Jr. (2000). Glucose depletion causes haploid invasive growth in yeast. Proc. Natl. Acad. Sci. USA 97: 13619-13624 [Abstract] [Full Text]  
  • Westfall, P. J., Momany, M. (2002). Aspergillus nidulans Septin AspB Plays Pre- and Postmitotic Roles in Septum, Branch, and Conidiophore Development. Mol. Biol. Cell 13: 110-118 [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»