Crk1, a novel Cdc2-related protein kinase, is required for hyphal development and virulence in Candida albicans.
Both mitogen-activated protein kinases and cyclin-dependent kinases play a role in hyphal development in Candida albicans. Using an oligonucleotide probe-based screen, we have isolated a new member of the Cdc2 kinase subfamily, designated Crk1 (Cdc2-related kinase). The protein sequence of Crk1 is most similar to those of Saccharomyces cerevisiae Sgv1 and human Pkl1/Cdk9. In S. cerevisiae, CRK1 suppresses some, but not all, of the defects associated with an sgv1 mutant. Deleting both copies of CRK1 in C. albicans slows growth slightly but leads to a profound defect in hyphal development under all conditions examined. crk1/crk1 mutants are impaired in the induction of hypha-specific genes and are avirulent in mice. Consistent with this, ectopic expression of the Crk1 kinase domain (CRK1N) promotes filamentous or invasive growth in S. cerevisiae and hyphal development in C. albicans. The activity of Crk1 in S. cerevisiae requires Flo8 but is independent of Ste12 and Phd1. Similarly, Crk1 promotes filamentation through a route independent of Cph1 and Efg1 in C. albicans. RAS1(V13) can also activate filamentation in a cph1/cph1 efg1/efg1 double mutant. Interestingly, CRK1N produces florid hyphae in ras1/ras1 strains, while RAS1(V13) generates feeble hyphae in crk1/crk1 strains.
Chen
J
J
State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry, Chinese Academy of Sciences, Shanghai 200031, China.
Zhou
S
S
Wang
Q
Q
Chen
X
X
Pan
T
T
Liu
H
H
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; D002176:Candida albicans / Q000166:cytology* / Q000235:genetics / Q000472:pathogenicity*; D002453:Cell Cycle; D002454:Cell Differentiation; D003001:Cloning, Molecular; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D017353:Gene Deletion; D005800:Genes, Fungal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D010675:Pheromones / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C100940:FLO8 protein, S cerevisaie; D005656:Fungal Proteins; D009687:Nuclear Proteins; C085984:PHD1 protein, S cerevisiae; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; D018844:Cyclin-Dependent Kinases; D020928:Mitogen-Activated Protein Kinases