原创力文档the polymorphic pseudokinase rop5 controls virulence in toxoplasma gondii by regulating the active kinase rop18的多态pseudokinase rop5控制毒性在调节活性激酶rop18刚地弓形虫.pdfVIP
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the polymorphic pseudokinase rop5 controls virulence in toxoplasma gondii by regulating the active kinase rop18的多态pseudokinase rop5控制毒性在调节活性激酶rop18刚地弓形虫
The Polymorphic Pseudokinase ROP5 Controls Virulence
in Toxoplasma gondii by Regulating the Active Kinase
ROP18
1. 1. 2 1 3,4
Michael S. Behnke , Sarah J. Fentress , Mona Mashayekhi , Lucy X. Li , Gregory A. Taylor , L.
David Sibley1*
1 Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America, 2 Department of Pathology and
Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America, 3 Departments of Medicine, Molecular Genetics and Microbiology,
and Immunology, Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina, United
States of America, 4 Geriatric Research, Education, and Clinical Center, VA Medical Center, Durham, North Carolina, United States of America
Abstract
Secretory 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-c 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 Drop5 and Drop18
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