TY - JOUR
T1 - Phosphoproteome of Cryptococcus neoformans
AU - Selvan, Lakshmi Dhevi N
AU - Renuse, Santosh
AU - Kaviyil, Jyothi Embekkat
AU - Sharma, Jyoti
AU - Pinto, Sneha M.
AU - Yelamanchi, Soujanya D.
AU - Puttamallesh, Vinuth N.
AU - Ravikumar, Raju
AU - Pandey, Akhilesh
AU - Prasad, T. S Keshava
AU - Harsha, H. C.
PY - 2014/1/31
Y1 - 2014/1/31
N2 - 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.
AB - 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.
KW - Fungal infection
KW - Metal oxide affinity chromatography
KW - Stress response
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U2 - 10.1016/j.jprot.2013.06.029
DO - 10.1016/j.jprot.2013.06.029
M3 - Article
C2 - 23851311
AN - SCOPUS:84892859415
SN - 1874-3919
VL - 97
SP - 287
EP - 295
JO - Journal of Proteomics
JF - Journal of Proteomics
ER -