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PMID: 12455960 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mating-type-specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans.

Eukaryotic cell ·Vol. 1 ·No. 2 ·2002-04-00 ·Pages 257-72

Wang P, Nichols CB, Lengeler KB, Cardenas ME, Cox GM, Perfect JR, Heitman J

Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving fusion of haploid MATalpha and MATa cells. Virulence has been linked to the mating type, and MATalpha cells are more virulent than congenic MATa cells. To study the link between the mating type and virulence, we functionally analyzed three genes encoding homologs of the p21-activated protein kinase family: STE20alpha, STE20a, and PAK1. In contrast to the STE20 genes that were previously shown to be in the mating-type locus, the PAK1 gene is unlinked to the mating type. The STE20alpha, STE20a, and PAK1 genes were disrupted in serotype A and D strains of C. neoformans, revealing central but distinct roles in mating, differentiation, cytokinesis, and virulence. ste20alpha pak1 and ste20a pak1 double mutants were synthetically lethal, indicating that these related kinases share an essential function. In summary, our studies identify an association between the STE20alpha gene, the MATalpha locus, and virulence in a serotype A clinical isolate and provide evidence that PAK kinases function in a MAP kinase signaling cascade controlling the mating, differentiation, and virulence of this fungal pathogen.

MeSH Terms
Alleles Amino Acid Sequence Animals Cell Division Cryptococcosis/microbiology Cryptococcus neoformans/enzymology,genetics,pathogenicity Female Fungal Proteins/classification,genetics,metabolism Haploidy MAP Kinase Signaling System/physiology Male Mice Models, Genetic Molecular Sequence Data Mutation Protein Kinases/genetics,physiology Protein Serine-Threonine Kinases/physiology Rabbits Recombination, Genetic Reproduction Sequence Alignment Serotyping Temperature Transcription Factors/classification,genetics,metabolism Virulence/physiology
Chemicals
Fungal Proteins Transcription Factors Protein Kinases protease activated kinase I Protein Serine-Threonine Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wang Ping
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nichols Connie B
Lengeler Klaus B
Cardenas Maria E
Cox Gary M
Perfect John R
Heitman Joseph
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Article Info
Journal
Eukaryotic cell
Abbr.
Eukaryot Cell
ISSN
1535-9778
DOI
10.1128/EC.1.2.257-272.2002
Published
2002-04-00
Pages
257-72
Language
English
Region
United States
NLM ID
101130731
PMCID
PMC118036
Subset
IM
Grants
NIAID NIH HHS · R37 AI039115 · United States
NIAID NIH HHS · R01 AI042159 · United States
NIAID NIH HHS · R01 AI42159 · United States
NIAID NIH HHS · R01 AI039115 · United States
NCI NIH HHS · K01 CA77075 · United States
NIAID NIH HHS · R01 AI39115 · United States
NIAID NIH HHS · P01 AI44975 · United States
NIAID NIH HHS · P01 AI044975 · United States
External Links
PubMed source DOI: 10.1128/EC.1.2.257-272.2002 PMC Full Text View journal details
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