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 Lamson, R. E.
Right arrow Articles by Pryciak, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lamson, R. E.
Right arrow Articles by Pryciak, P. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2002, p. 2939-2951, Vol. 22, No. 9
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.9.2939-2951.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Cdc42 Regulation of Kinase Activity and Signaling by the Yeast p21-Activated Kinase Ste20

Rachel E. Lamson, Matthew J. Winters, and Peter M. Pryciak*

Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605

Received 3 December 2001/ Returned for modification 24 January 2002/ Accepted 4 February 2002

The Saccharomyces cerevisiae kinase Ste20 is a member of the p21-activated kinase (PAK) family with several functions, including pheromone-responsive signal transduction. While PAKs are usually activated by small G proteins and Ste20 binds Cdc42, the role of Cdc42-Ste20 binding has been controversial, largely because Ste20 lacking its entire Cdc42-binding (CRIB) domain retains kinase activity and pheromone response. Here we show that, unlike CRIB deletion, point mutations in the Ste20 CRIB domain that disrupt Cdc42 binding also disrupt pheromone signaling. We also found that Ste20 kinase activity is stimulated by GTP-bound Cdc42 in vivo and this effect is blocked by the CRIB point mutations. Moreover, the Ste20 CRIB and kinase domains bind each other, and mutations that disrupt this interaction cause hyperactive kinase activity and bypass the requirement for Cdc42 binding. These observations demonstrate that the Ste20 CRIB domain is autoinhibitory and that this negative effect is antagonized by Cdc42 to promote Ste20 kinase activity and signaling. Parallel results were observed for filamentation pathway signaling, suggesting that the requirement for Cdc42-Ste20 interaction is not qualitatively different between the mating and filamentation pathways. While necessary for pheromone signaling, the role of the Cdc42-Ste20 interaction does not require regulation by pheromone or the pheromone-activated Gß{gamma} complex, because the CRIB point mutations also disrupt signaling by activated forms of the kinase cascade scaffold protein Ste5. In total, our observations indicate that Cdc42 converts Ste20 to an active form, while pathway stimuli regulate the ability of this active Ste20 to trigger signaling through a particular pathway.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 377 Plantation St., Four Biotech, Rm. 334, Worcester, MA 01605. Phone: (508) 856-8756. Fax: (508) 856-8774. E-mail: peter.pryciak{at}umassmed.edu.

Molecular and Cellular Biology, May 2002, p. 2939-2951, Vol. 22, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.9.2939-2951.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bartholomew, C. R., Hardy, C. F. J. (2009). p21-Activated Kinases Cla4 and Ste20 Regulate Vacuole Inheritance in Saccharomyces cerevisiae. Eukaryot Cell 8: 560-572 [Abstract] [Full Text]  
  • Garrenton, L. S., Braunwarth, A., Irniger, S., Hurt, E., Kunzler, M., Thorner, J. (2009). Nucleus-Specific and Cell Cycle-Regulated Degradation of Mitogen-Activated Protein Kinase Scaffold Protein Ste5 Contributes to the Control of Signaling Competence. Mol. Cell. Biol. 29: 582-601 [Abstract] [Full Text]  
  • Annan, R. B., Wu, C., Waller, D. D., Whiteway, M., Thomas, D. Y. (2008). Rho5p Is Involved in Mediating the Osmotic Stress Response in Saccharomyces cerevisiae, and Its Activity Is Regulated via Msi1p and Npr1p by Phosphorylation and Ubiquitination. Eukaryot Cell 7: 1441-1449 [Abstract] [Full Text]  
  • Yu, L., Qi, M., Sheff, M. A., Elion, E. A. (2008). Counteractive Control of Polarized Morphogenesis during Mating by Mitogen-activated Protein Kinase Fus3 and G1 Cyclin-dependent Kinase. Mol. Biol. Cell 19: 1739-1752 [Abstract] [Full Text]  
  • Kawasaki, L., Castaneda-Bueno, M., Sanchez-Paredes, E., Velazquez-Zavala, N., Torres-Quiroz, F., Ongay-Larios, L., Coria, R. (2008). Protein Kinases Involved in Mating and Osmotic Stress in the Yeast Kluyveromyces lactis. Eukaryot Cell 7: 78-85 [Abstract] [Full Text]  
  • Strickfaden, S. C., Pryciak, P. M. (2008). Distinct Roles for Two G{alpha} G Interfaces in Cell Polarity Control by a Yeast Heterotrimeric G Protein. Mol. Biol. Cell 19: 181-197 [Abstract] [Full Text]  
  • Takahashi, S., Pryciak, P. M. (2007). Identification of Novel Membrane-binding Domains in Multiple Yeast Cdc42 Effectors. Mol. Biol. Cell 18: 4945-4956 [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]  
  • Heinrich, M., Kohler, T., Mosch, H.-U. (2007). Role of Cdc42-Cla4 Interaction in the Pheromone Response of Saccharomyces cerevisiae. Eukaryot Cell 6: 317-327 [Abstract] [Full Text]  
  • Yamaguchi, Y., Ota, K., Ito, T. (2007). A Novel Cdc42-interacting Domain of the Yeast Polarity Establishment Protein Bem1: IMPLICATIONS FOR MODULATION OF MATING PHEROMONE SIGNALING. J. Biol. Chem. 282: 29-38 [Abstract] [Full Text]  
  • Garrenton, L. S., Young, S. L., Thorner, J. (2006). Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain. Genes Dev. 20: 1946-1958 [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]  
  • Winters, M. J., Pryciak, P. M. (2005). Interaction with the SH3 Domain Protein Bem1 Regulates Signaling by the Saccharomyces cerevisiae p21-Activated Kinase Ste20. Mol. Cell. Biol. 25: 2177-2190 [Abstract] [Full Text]  
  • Gruhler, A., Olsen, J. V., Mohammed, S., Mortensen, P., Faergeman, N. J., Mann, M., Jensen, O. N. (2005). Quantitative Phosphoproteomics Applied to the Yeast Pheromone Signaling Pathway. Mol. Cell. Proteomics 4: 310-327 [Abstract] [Full Text]  
  • Cullen, P. J., Sabbagh, W. Jr., Graham, E., Irick, M. M., van Olden, E. K., Neal, C., Delrow, J., Bardwell, L., Sprague, G. F. Jr. (2004). A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth pathway in yeast. Genes Dev. 18: 1695-1708 [Abstract] [Full Text]  
  • Wild, A. C., Yu, J. W., Lemmon, M. A., Blumer, K. J. (2004). The p21-activated Protein Kinase-related Kinase Cla4 Is a Coincidence Detector of Signaling by Cdc42 and Phosphatidylinositol 4-Phosphate. J. Biol. Chem. 279: 17101-17110 [Abstract] [Full Text]  
  • Dong, Y., Pruyne, D., Bretscher, A. (2003). Formin-dependent actin assembly is regulated by distinct modes of Rho signaling in yeast. JCB 161: 1081-1092 [Abstract] [Full Text]  
  • Bassilana, M., Blyth, J., Arkowitz, R. A. (2003). Cdc24, the GDP-GTP Exchange Factor for Cdc42, Is Required for Invasive Hyphal Growth of Candida albicans. Eukaryot Cell 2: 9-18 [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»