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J Proteomics. 2014 Jan 31;97:287-95. doi: 10.1016/j.jprot.2013.06.029. Epub 2013 Jul 11.

Phosphoproteome of Cryptococcus neoformans.

Author information

1
Institute of Bioinformatics, International Technology Park, Bangalore 560 066, India; Amrita School of Biotechnology, Amrita University, Kollam 690 525, India.
2
Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India.
3
Institute of Bioinformatics, International Technology Park, Bangalore 560 066, India; Manipal University, Madhav Nagar, Manipal, Karnataka 576104, India.
4
Institute of Bioinformatics, International Technology Park, Bangalore 560 066, India.
5
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: pandey@jhmi.edu.
6
Institute of Bioinformatics, International Technology Park, Bangalore 560 066, India; Amrita School of Biotechnology, Amrita University, Kollam 690 525, India; Manipal University, Madhav Nagar, Manipal, Karnataka 576104, India. Electronic address: keshav@ibioinformatics.org.
7
Institute of Bioinformatics, International Technology Park, Bangalore 560 066, India. Electronic address: harsha@ibioinformatics.org.

Abstract

Cryptococcus neoformans is an encapsulated pathogenic yeast, which causes life threatening meningitis in immunocompromised individuals. C. neoformans var. grubii is the most prevalent and virulent form among the two varieties of C. neoformans - C. neoformans var. grubii and C. neoformans var. neoformans. The virulence of C. neoformans is mainly conferred by its capsule and melanin. cAMP dependent PKA-induced phosphorylation events are reported to be associated with the expression of these virulence traits, which highlights the importance of phosphoproteins in virulence and infection. Therefore, we performed global profiling of phosphoproteome of C. neoformans to enable a better understanding of molecular regulation of its virulence and pathogenesis. High resolution mass spectrometry of TiO2 enriched phosphopeptides from C. neoformans var. grubii grown in culture led to the identification of 1089 phosphopeptides derived from 648 proteins including about 45 kinases. Motif enrichment analysis revealed that most CDK family substrates were found to be phosphorylated. This indicates that cyclin-dependent kinases were among the active kinases in the pathogen in culture. These studies provide a framework for understanding virulence mechanisms in the context of signalling pathways in pathogenic yeast. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.

BIOLOGICAL SIGNIFICANCE:

C. neoformans is a pathogenic yeast responsible for cryptococcal meningitis. Melanin and polysaccharide capsule have been established as some of the key virulence factors that play a major role in the pathogenesis of C. neoformans. Recent studies have shown the role of kinase mediated signalling pathways in governing biosynthesis of these virulence factors. This study revealed 1540 phosphorylation sites in 648 proteins providing a comprehensive view of phosphoproteins in C. neoformans. This should serve as a useful resource to explore activated signalling pathways in C. neoformans and their association with its virulence and pathogenesis.

KEYWORDS:

Basic pH reversed-phase liquid chromatography.; CID; Collision induced dissociation; ETD; Electron transfer dissociation; Fungal infection; Metal oxide affinity chromatography; Stress response; TiO(2); Titanium dioxide; bRPLC

PMID:
23851311
DOI:
10.1016/j.jprot.2013.06.029
[Indexed for MEDLINE]
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