![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on July 1, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 7, 2006
Revised on April 19, 2006
Accepted on April 21, 2006
Departments of *Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
Monitoring Editor: Peter Walter
The stress-activated MAPK pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cryptococcus neoformans uniquely uses the stress-activated Pbs2-Hog1 MAPK system to govern a plethora of cellular events, including stress-responses, drug sensitivity, sexual reproduction, and virulence. Here, we characterized a fungal "two-component" system that controls these fundamental cellular functions via the Pbs2-Hog1 MAPK cascade. A typical response regulator, Ssk1, modulated all Hog1-dependent phenotypes by controlling Hog1 phosphorylation, indicating that Ssk1 is the major upstream signaling component of the Pbs2-Hog1 pathway. A second response regulator, Skn7, governs sensitivity to Na+ ions and the antifungal agent fludioxonil, negatively controls melanin production, and functions independently of Hog1 regulation. To control these response regulators, C. neoformans utilizes multiple sensor kinases, including Tco1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug-sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. Our findings highlight unique adaptations of this global two-component-MAPK signaling cascade in a ubiquitous human fungal pathogen.
Present address: Department of Bioinformatics and Life Science, Soongsil University, Seoul, Korea 156-743.
Address correspondence to:
Joseph Heitman (heitm001{at}duke.edu)
This article has been cited by other articles:
|
|
 |
|
  N. Chauhan and R. Calderone Two-Component Signal Transduction Proteins as Potential Drug Targets in Medically Important Fungi Infect. Immun., November 1, 2008; 76(11): 4795 - 4803. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ruprich-Robert, F. Chapeland-Leclerc, S. Boisnard, M. Florent, G. Bories, and N. Papon Contributions of the Response Regulators Ssk1p and Skn7p in the Pseudohyphal Development, Stress Adaptation, and Drug Sensitivity of the Opportunistic Yeast Candida lusitaniae Eukaryot. Cell, June 1, 2008; 7(6): 1071 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Cowen and W. J. Steinbach Stress, Drugs, and Evolution: the Role of Cellular Signaling in Fungal Drug Resistance Eukaryot. Cell, May 1, 2008; 7(5): 747 - 764. [Full Text] [PDF]
|
|
|
|
|
|
Y.-S. Bahn, S. Geunes-Boyer, and J. Heitman Ssk2 Mitogen-Activated Protein Kinase Kinase Kinase Governs Divergent Patterns of the Stress-Activated Hog1 Signaling Pathway in Cryptococcus neoformans Eukaryot. Cell, December 1, 2007; 6(12): 2278 - 2289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Cheetham, D. A. Smith, A. da Silva Dantas, K. S. Doris, M. J. Patterson, C. R. Bruce, and J. Quinn A Single MAPKKK Regulates the Hog1 MAPK Pathway in the Pathogenic Fungus Candida albicans Mol. Biol. Cell, November 1, 2007; 18(11): 4603 - 4614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Chapeland-Leclerc, P. Paccallet, G. Ruprich-Robert, D. Reboutier, C. Chastin, and N. Papon Differential Involvement of Histidine Kinase Receptors in Pseudohyphal Development, Stress Adaptation, and Drug Sensitivity of the Opportunistic Yeast Candida lusitaniae Eukaryot. Cell, October 1, 2007; 6(10): 1782 - 1794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhao, R. Mehrabi, and J.-R. Xu Mitogen-Activated Protein Kinase Pathways and Fungal Pathogenesis Eukaryot. Cell, October 1, 2007; 6(10): 1701 - 1714. [Full Text] [PDF]
|
|
|
|
|
|
I. Vargas-Perez, O. Sanchez, L. Kawasaki, D. Georgellis, and J. Aguirre Response Regulators SrrA and SskA Are Central Components of a Phosphorelay System Involved in Stress Signal Transduction and Asexual Sporulation in Aspergillus nidulans Eukaryot. Cell, September 1, 2007; 6(9): 1570 - 1583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Jones, S. E. Greer-Phillips, and K. A. Borkovich The Response Regulator RRG-1 Functions Upstream of a Mitogen-activated Protein Kinase Pathway Impacting Asexual Development, Female Fertility, Osmotic Stress, and Fungicide Resistance in Neurospora crassa Mol. Biol. Cell, June 1, 2007; 18(6): 2123 - 2136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Eliahu, A. Igbaria, M. S. Rose, B. A. Horwitz, and S. Lev Melanin Biosynthesis in the Maize Pathogen Cochliobolus heterostrophus Depends on Two Mitogen-Activated Protein Kinases, Chk1 and Mps1, and the Transcription Factor Cmr1 Eukaryot. Cell, March 1, 2007; 6(3): 421 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Izumitsu, A. Yoshimi, and C. Tanaka Two-Component Response Regulators Ssk1p and Skn7p Additively Regulate High-Osmolarity Adaptation and Fungicide Sensitivity in Cochliobolus heterostrophus Eukaryot. Cell, February 1, 2007; 6(2): 171 - 181. [Abstract] [Full Text] [PDF]
|
|
