The two isoforms of the cAMP-dependent protein kinase catalytic subunit are involved in the control of dimorphism in the human fungal pathogen Candida albicans.

CLOUTIER, MONICKA-CASTILLA, ROCÍO; BOLDUC, NATHALIE; ZELADA, ALICIA; MARTINEAU, PHILIPPE; BOULLION, MARLENE; MAGEE, BEATRICE B; PASSERON, SUSANA; GIASSON, LUC; CANTORE, MARIA L.

FUNGAL GENETICS AND BIOLOGY

Academic Press

Lugar: Estados Unidos; Año: 2003 vol. 38 p. 133 - 141

1087-1845

We have cloned the Candida albicans TPK2 gene encoding a cAMP-dependent protein kinase (PKA) catalytic subunit and generated a tpk2 homozygous null mutant to assess its ability to germinate in liquid media. N-acetylglucosamine (GlcNAc) induced germ-tube formation was  attenuated in the tpk2 strain and enhanced by compounds that are known to increase the PKA activity in situ. Germination was completely blocked in the presence of the myristoylated derivative of the heat-stable PKA inhibitor (MyrPKI). These results indicate that the other isoform of the catalytic subunit of PKA (Tpk1p) is able to support filamentous growth in the absence of the TPK2 gene. We demonstrated the expression of the second catalytically active form of PKA in both wild-type and tpk2 yeast cells. The PKA activity measured in the mutant lacking the TPK2 gene was about 10% of that displayed by the wild type. Our results are consistent with a model in which TPK1 acts positively in regulating the morphogenetic transition in C. albicans. Analysis of the germinative response of both the wild-type and tpk2 null mutant strains to different serum concentrations showed that germ-tube formation is impaired in the tpk2 only at low serum concentrations (0.5-2.5%). This result suggests an interrelation between serum and PKA-mediated signalling pathways only revealed at low serum concentrations.