{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:35:41Z","timestamp":1779341741948,"version":"3.51.4"},"reference-count":71,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,10,5]]},"abstract":"<jats:p>Neisseria gonorrhoeae (Ngo), the etiologic agent of gonorrhea, induce a number of proinflammatory cytokines by contact to epithelial cells. Cytokine genes and a variety of other immune response genes are activated as a result of the regulatory function of immediate early response transcription factors including activator protein 1 (AP-1). Since it is established that phosphorylation of c-Jun, the central component of AP-1, by the stress-activated c-Jun NH2-terminal kinase (JNK) increases the transcriptional activity of AP-1, we studied whether Ngo could induce stress response pathways involving JNK. We found that virulent Ngo strains induce phosphorylation and activation of JNK but not of p38 kinase. Analysis of a nonpathogenic Ngo strain revealed only weak JNK activation. In respect to the molecular components upstream of the JNK signaling cascade, we show that a dominant negative mutant of MAP kinase kinase 4 (MKK4) represses transcription of an AP-1\u2013dependent reporter gene. Regarding upstream stress response factors involved in Ngo-induced MKK4\/JNK\/AP-1 activation, we identified p21-activated kinase (PAK) but not MAPK\/ERK kinase kinase (MEKK1). Inhibition of small GTPases including Rac1 and Cdc42 by Toxin B prevented JNK and AP-1 activation. Our results indicate that Ngo induce the activation of proinflammatory cytokines via a cascade of cellular stress response kinases involving PAK, which directs the signal from the Rho family of small GTPases to JNK\/AP-1 activation.<\/jats:p>","DOI":"10.1084\/jem.188.7.1277","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"1277-1286","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["Coordinate Activation of Activator Protein 1 and Inflammatory Cytokines in Response to <i>Neisseria gonorrhoeae<\/i> Epithelial Cell Contact Involves Stress Response Kinases"],"prefix":"10.1084","volume":"188","author":[{"given":"Michael","family":"Naumann","sequence":"first","affiliation":[{"name":"From the *Max-Planck-Institut f\u00fcr Infektionsbiologie, Abteilung Molekulare Biologie, 10117 Berlin, Germany; and \u2021Max-Planck-Institut f\u00fcr Biologie, Abteilung Infektionsbiologie, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Rudel","sequence":"additional","affiliation":[{"name":"From the *Max-Planck-Institut f\u00fcr Infektionsbiologie, Abteilung Molekulare Biologie, 10117 Berlin, Germany; and \u2021Max-Planck-Institut f\u00fcr Biologie, Abteilung Infektionsbiologie, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"Wieland","sequence":"additional","affiliation":[{"name":"From the *Max-Planck-Institut f\u00fcr Infektionsbiologie, Abteilung Molekulare Biologie, 10117 Berlin, Germany; and \u2021Max-Planck-Institut f\u00fcr Biologie, Abteilung Infektionsbiologie, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia","family":"Bartsch","sequence":"additional","affiliation":[{"name":"From the *Max-Planck-Institut f\u00fcr Infektionsbiologie, Abteilung Molekulare Biologie, 10117 Berlin, Germany; and \u2021Max-Planck-Institut f\u00fcr Biologie, Abteilung Infektionsbiologie, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas F.","family":"Meyer","sequence":"additional","affiliation":[{"name":"From the *Max-Planck-Institut f\u00fcr Infektionsbiologie, Abteilung Molekulare Biologie, 10117 Berlin, Germany; and \u2021Max-Planck-Institut f\u00fcr Biologie, Abteilung Infektionsbiologie, 72076 T\u00fcbingen, Germany"},{"name":"From the *Max-Planck-Institut f\u00fcr Infektionsbiologie, Abteilung Molekulare Biologie, 10117 Berlin, Germany; and \u2021Max-Planck-Institut f\u00fcr Biologie, Abteilung Infektionsbiologie, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1998,10,5]]},"reference":[{"key":"2023072508195801100_B1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/S0966-842X(00)88941-6","article-title":"Epithelial cytokine responses and mucosal cytokine networks","volume":"3","author":"Hedges","year":"1995","journal-title":"Trends Microbiol"},{"key":"2023072508195801100_B2","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1126\/science.274.5290.1194","article-title":"Ultraviolet light and osmotic stress\u2014activation of the JNK cascade through multiple growth factor and cytokine receptors","volume":"274","author":"Rosette","year":"1996","journal-title":"Science"},{"key":"2023072508195801100_B3","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1084\/jem.186.2.247","article-title":"Neisseria gonorrheaeepithelial cell interaction leads to the activation of the transcription factors nuclear factor \u03baB and activator protein 1 and the induction of inflammatory cytokines","volume":"186","author":"Naumann","year":"1997","journal-title":"J Exp Med"},{"key":"2023072508195801100_B4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1099\/00222615-9-1-1","article-title":"Resistance of Neisseria gonorrhoeaeto ingestion and digestion by phagocytes of human buffy coat","volume":"9","author":"Witt","year":"1976","journal-title":"J Med Microbiol"},{"key":"2023072508195801100_B5","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/infdis\/143.3.413","article-title":"Pathogenic mechanisms of Neisseria gonorrhoeae: observation on damage to human fallopian tubes in organ culture by gonococci of colony type 1 or type 4","volume":"143","author":"McGee","year":"1981","journal-title":"J Infect Dis"},{"key":"2023072508195801100_B6","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1128\/jb.85.6.1274-1279.1963","article-title":"Neisseria gonorrhoeae. 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