The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18

dc.contributor.authorBehnke, Michael S.
dc.contributor.authorFentress, Sarah J.
dc.contributor.authorMashayekhi, Mona
dc.contributor.authorLi, Lucy X.
dc.contributor.authorTaylor, Gregory A.
dc.contributor.authorSibley, L. David
dc.date.accessioned2019-04-22T19:34:36Z
dc.date.available2019-04-22T19:34:36Z
dc.date.issued2012-11
dc.description.abstractSecretory polymorphic serine/threonine kinases control pathogenesis of Toxoplasma gondii in the mouse. Genetic studies show that the pseudokinase ROP5 is essential for acute virulence, but do not reveal its mechanism of action. Here we demonstrate that ROP5 controls virulence by blocking IFN-γ mediated clearance in activated macrophages. ROP5 was required for the catalytic activity of the active S/T kinase ROP18, which phosphorylates host immunity related GTPases (IRGs) and protects the parasite from clearance. ROP5 directly regulated activity of ROP18 in vitro, and both proteins were necessary to avoid IRG recruitment and clearance in macrophages. Clearance of both the Δrop5 and Δrop18 mutants was reversed in macrophages lacking Irgm3, which is required for IRG function, and the virulence defect was fully restored in Irgm3−/− mice. Our findings establish that the pseudokinase ROP5 controls the activity of ROP18, thereby blocking IRG mediated clearance in macrophages. Additionally, ROP5 has other functions that are also Irgm3 and IFN-γ dependent, indicting it plays a general role in governing virulence factors that block immunity.en_US
dc.description.sponsorshipNational Institutes of Health grants AI036629, AIAI082423en_US
dc.identifier.citationBehnke, Michael S., Sarah J. Fentress, Mona Mashayekhi, Lucy X. Li, Gregory A. Taylor, and L. David Sibley. “The Polymorphic Pseudokinase ROP5 Controls Virulence in Toxoplasma Gondii by Regulating the Active Kinase ROP18.” PLoS Pathogens 8, no. 11 (November 8, 2012): e1002992. doi:10.1371/journal.ppat.1002992.en_US
dc.identifier.issn1553-7374
dc.identifier.urihttps://scholarworks.montana.edu/handle/1/15458
dc.language.isoenen_US
dc.rightsCC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.titleThe polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18en_US
dc.typeArticleen_US
mus.citation.issue11en_US
mus.citation.journaltitlePLoS Pathogensen_US
mus.citation.volume8en_US
mus.data.thumbpage9en_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.identifier.doi10.1371/journal.ppat.1002992en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.researchgroupMT INBRE Bioinformatics and Biostatistics Core.en_US
mus.relation.universityMontana State University - Bozemanen_US

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Behnke_PLoSpathogens_2012.PDF
Size:
2 MB
Format:
Adobe Portable Document Format
Description:
The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18 (PDF)
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
826 B
Format:
Item-specific license agreed upon to submission
Description:
Copyright (c) 2002-2022, LYRASIS. All rights reserved.