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Eukaryot Cell

Title:		Mating-type-specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans
Author(s):		Wang P; Nichols CB; Lengeler KB; Cardenas ME; Cox GM; Perfect JR; Heitman J;
Address:		"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA"
Journal Title:		Eukaryot Cell
Year:		2002
Volume:		1
Issue:		2
Page Number:		257 - 272
DOI:		10.1128/EC.1.2.257-272.2002
ISSN/ISBN:		1535-9778 (Print) 1535-9786 (Electronic) 1535-9786 (Linking)
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"
Keywords:		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 Mo;
Notes:		"MedlineWang, Ping Nichols, Connie B Lengeler, Klaus B Cardenas, Maria E Cox, Gary M Perfect, John R Heitman, Joseph eng R37 AI039115/AI/NIAID NIH HHS/ R01 AI042159/AI/NIAID NIH HHS/ R01 AI42159/AI/NIAID NIH HHS/ R01 AI039115/AI/NIAID NIH HHS/ K01 CA77075/CA/NCI NIH HHS/ R01 AI39115/AI/NIAID NIH HHS/ P01 AI44975/AI/NIAID NIH HHS/ P01 AI044975/AI/NIAID NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2002/11/29 Eukaryot Cell. 2002 Apr; 1(2):257-72. doi: 10.1128/EC.1.2.257-272.2002"