Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses

Lucia Peixoto; Feng Chen; Omar S Harb; Paul H Davis; Daniel P Beiting; Catie Small Brownback; Dinkorma Ouloguem; David S Roos

doi:10.1016/j.chom.2010.07.004

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Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses

Journal article

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Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses

Lucia Peixoto, Feng Chen, Omar S Harb, Paul H Davis, Daniel P Beiting, Catie Small Brownback, Dinkorma Ouloguem and David S Roos

Cell host & microbe, Vol.8(2), pp.208-218

08/19/2010

DOI: https://doi.org/10.1016/j.chom.2010.07.004

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https://hdl.handle.net/2376/109386

PMCID: PMC2963626

PMID: 20709297

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https://doi.org/10.1016/j.chom.2010.07.004View

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Abstract

Cell Line

Membrane Proteins - genetics

Down-Regulation

Genomics

Humans

Toxoplasma - physiology

Protozoan Proteins - genetics

Toxoplasma - enzymology

Toxoplasmosis - parasitology

Proteins - genetics

Animals

Toxoplasma - genetics

Fibroblasts - parasitology

Host-Parasite Interactions

Phosphotransferases - genetics

Fibroblasts - metabolism

Apicomplexan parasites release factors via specialized secretory organelles (rhoptries, micronemes) that are thought to control host cell responses. In order to explore parasite-mediated modulation of host cell signaling pathways, we exploited a phylogenomic approach to characterize the Toxoplasma gondii kinome, defining a 44 member family of coccidian-specific secreted kinases, some of which have been previously implicated in virulence. Comparative genomic analysis suggests that "ROPK" genes are under positive selection, and expression profiling demonstrates that most are differentially expressed between strains and/or during differentiation. Integrating diverse genomic-scale analyses points to ROP38 as likely to be particularly important in parasite biology. Upregulating expression of this previously uncharacterized gene in transgenic parasites dramatically suppresses transcriptional responses in the infected cell. Specifically, parasite ROP38 downregulates host genes associated with MAPK signaling and the control of apoptosis and proliferation. These results highlight the value of integrative genomic approaches in prioritizing candidates for functional validation.

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Title: Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses
Creators: Lucia Peixoto - Department of Biology and Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Feng Chen
Omar S Harb
Paul H Davis
Daniel P Beiting
Catie Small Brownback
Dinkorma Ouloguem
David S Roos
Publication Details: Cell host & microbe, Vol.8(2), pp.208-218
Academic Unit: Biomedical Sciences, Department of
Publisher: United States
Grant note: AI077268 / NIAID NIH HHS AI28724 / NIAID NIH HHS F32 AI075846 / NIAID NIH HHS R37 AI028724 / NIAID NIH HHS F32 AI077268 / NIAID NIH HHS RR016469 / NCRR NIH HHS AI075846 / NIAID NIH HHS P20 RR016469 / NCRR NIH HHS R37 AI028724-17 / NIAID NIH HHS
Identifiers: 99900547247401842
Language: English
Resource Type: Journal article