title: The Yersinia effector protein YpkA induces apoptosis independently of actin depolymerization.
abstract: The pathogenicity of the plague agent Yersinia pestis is largely due to the injection of effector proteins that potently block immune responses into host cells through a type III secretion apparatus. One Yersinia effector protein, YpkA, a putative serine/threonine kinase, has been reported to act by depolymerizing actin and disrupting actin microfilament organization. Using YpkA-GFP fusion proteins to directly visualize cells expressing YpkA, we found instead that YpkA triggered rapid cell death that can be blocked by caspase inhibitors and Bcl-xL, but was not dependent on caspase-8. The actin depolymerization promoted by YpkA was only seen in cells with other features of apoptosis, and was blocked by inhibiting apoptosis, indicating that actin filament disruption is likely to be a result, rather than a cause of YpkA-induced apoptosis. A region including aa 133-262 in YpkA was sufficient for inducing apoptosis independent of localization to the plasma membrane. These data suggest that YpkA can act as a direct inducer of cell death.
authors.affiliation: Molecular Immunology and Inflammation Branch, Immunoregulation Unit, National Institute and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Heiyoung
authors.initials: H
authors.lastname: Park
authors.forename: Kabir
authors.initials: K
authors.lastname: Teja
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
authors.forename: Richard M
authors.initials: RM
authors.lastname: Siegel
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D053181:Caspase 8 / Q000502:physiology; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015010:Yersinia pestis / Q000235:genetics / Q000276:immunology*
chemical_list: D000199:Actins; D001426:Bacterial Proteins; C079893:ypkA protein, Yersinia; D017346:Protein Serine-Threonine Kinases; D053181:Caspase 8