{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:13:09Z","timestamp":1792735989799,"version":"4.5.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"33","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,8,18]]},"abstract":"<jats:p>\n                    NF-\u03baB is critical in innate immune defense responses against invading microbial pathogens.\n                    <jats:italic>Legionella pneumophila<\/jats:italic>\n                    infection of lung macrophages causes Legionnaire's disease with pneumonia symptoms. A set of NF-\u03baB-controlled genes involved in inflammation and anti-apoptosis are up-regulated in macrophages upon\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    infection in a\n                    <jats:italic>Legionella<\/jats:italic>\n                    Dot\/Icm type IV secretion system-dependent manner. Among \u2248100 Dot\/Icm substrates screened, we identified LegK1 as the sole\n                    <jats:italic>Legionella<\/jats:italic>\n                    protein that harbors a highly potent NF-\u03baB-stimulating activity. LegK1 does not affect MAPK and IFN pathways. Activation of the NF-\u03baB pathway by LegK1 requires its eukaryotic-like Ser\/Thr kinase activity and is independent of upstream components in the NF-\u03baB pathway, including TRAFs, NIK, MEKK3, and TAK1. Cell-free reconstitution revealed that LegK1 stimulated NF-\u03baB activation in the absence of IKK\u03b1 and IKK\u03b2, and LegK1 efficiently phosphorylated I\u03baB\u03b1 on Ser-32 and Ser-36 both in vitro and in cells. LegK1 seems to mimic the host IKK as LegK1 also directly phosphorylated other I\u03baB family of inhibitors including p100 in the noncanonical NF-\u03baB pathway. Phosphorylation of p100 by LegK1 led to its maturation into p52. Thus, LegK1 is a bacterial effector that directly activates the host NF-\u03baB signaling and likely plays important roles in modulating macrophage defense or inflammatory responses during\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    infection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0907200106","type":"journal-article","created":{"date-parts":[[2009,8,3]],"date-time":"2009-08-03T21:43:30Z","timestamp":1249335810000},"page":"13725-13730","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":178,"title":["A\n                    <i>Legionella<\/i>\n                    type IV effector activates the NF-\u03baB pathway by phosphorylating the I\u03baB family of inhibitors"],"prefix":"10.1073","volume":"106","author":[{"given":"Jianning","family":"Ge","sequence":"first","affiliation":[{"name":"College of Life Sciences, Beijing Normal University, Beijing 100875, China; and"},{"name":"National Institute of Biological Sciences, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Beijing Normal University, Beijing 100875, China; and"},{"name":"National Institute of Biological Sciences, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[{"name":"National Institute of Biological Sciences, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Beijing Normal University, Beijing 100875, China; and"},{"name":"National Institute of Biological Sciences, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Beijing Normal University, Beijing 100875, China; and"},{"name":"National Institute of Biological Sciences, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Li","sequence":"additional","affiliation":[{"name":"National Institute of Biological Sciences, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Liu","sequence":"additional","affiliation":[{"name":"National Institute of Biological Sciences, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Shao","sequence":"additional","affiliation":[{"name":"National Institute of Biological Sciences, Beijing 102206, 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