Crk1, a Novel Cdc2-Related Protein Kinase, Is Required for Hyphal Development and Virulence in Candida albicans

Author:

Chen Jiangye12,Zhou Song1,Wang Qin1,Chen Xi1,Pan Ting2,Liu Haoping2

Affiliation:

1. State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry, Chinese Academy of Sciences, Shanghai 200031, China, 1 and

2. Department of Biological Chemistry, College of Medicine, University of California, Irvine, Irvine, California 92697-17002

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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