{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:01:33Z","timestamp":1791252093854,"version":"4.1.0"},"reference-count":64,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:p> We showed previously that enteropathogenic Escherichia coli (EPEC) infection of intestinal epithelial cells induces inflammation by activating NF-\u03baB and upregulating IL-8 expression. We also reported that extracellular signal-regulated kinases (ERKs) participate in EPEC-induced NF-\u03baB activation but that other signaling molecules such as PKC\u03b6 may be involved. The aim of this study was to determine whether PKC\u03b6 is activated by EPEC and to investigate whether it also plays a role in EPEC-associated inflammation. EPEC infection induced the translocation of PKC\u03b6 from the cytosol to the membrane and its activation as determined by kinase activity assays. Inhibition of PKC\u03b6 by the pharmacological inhibitor rottlerin, the inhibitory myristoylated PKC\u03b6 pseudosubstrate (MYR-PKC\u03b6-PS), or transient expression of a nonfunctional PKC\u03b6 significantly suppressed EPEC-induced I\u03baB\u03b1 phosphorylation. Although PKC\u03b6 can activate ERK, MYR-PKC\u03b6-PS had no effect on EPEC-induced stimulation of this pathway, suggesting that they are independent events. PKC\u03b6 can regulate NF-\u03baB activation by interacting with and activating I\u03baB kinase (IKK). Coimmunoprecipitation studies showed that the association of PKC\u03b6 and IKK increased threefold 60 min after infection. Kinase activity assays using immunoprecipitated PKC\u03b6-IKK complexes from infected intestinal epithelial cells and recombinant I\u03baB\u03b1 as a substrate showed a 2.5-fold increase in I\u03baB\u03b1 phosphorylation. PKC\u03b6 can also regulate NF-\u03baB by serine phosphorylation of the p65 subunit. Serine phosphorylation of p65 was increased after EPEC infection but could not be consistently attenuated by MYR-PKC\u03b6-PS, suggesting that other signaling events may be involved in this particular arm of NF-\u03baB regulation. We speculate that EPEC infection of intestinal epithelial cells activates several signaling pathways including PKC\u03b6 and ERK that lead to NF-\u03baB activation, thus ensuring the proinflammatory response. <\/jats:p>","DOI":"10.1152\/ajpcell.00444.2002","type":"journal-article","created":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T00:16:02Z","timestamp":1368490562000},"page":"C512-C521","source":"Crossref","is-referenced-by-count":56,"title":["PKC\u03b6 participates in activation of inflammatory response induced by  enteropathogenic <i>E. coli<\/i>"],"prefix":"10.1152","volume":"285","author":[{"given":"Suzana D.","family":"Savkovic","sequence":"first","affiliation":[{"name":"Section of Digestive Diseases and Nutrition, Department of Medicine,  University of Illinois, West Side Department of Veterans Affairs Medical  Center, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasia","family":"Koutsouris","sequence":"additional","affiliation":[{"name":"Section of Digestive Diseases and Nutrition, Department of Medicine,  University of Illinois, West Side Department of Veterans Affairs Medical  Center, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"Hecht","sequence":"additional","affiliation":[{"name":"Section of Digestive Diseases and Nutrition, Department of Medicine,  University of Illinois, West Side Department of Veterans Affairs Medical  Center, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"crossref","unstructured":"Anrather J,  Csizmadia V, Soares MP, and Winkler H. Regulation of NF-kappaB RelA  phosphorylation and transcriptional activity by p21(ras) and protein kinase  Czeta in primary endothelial cells. J Biol Chem 274: 13594\u201313603,  1999.","DOI":"10.1074\/jbc.274.19.13594"},{"key":"REF2","doi-asserted-by":"crossref","unstructured":"Bain C, Keller  R, Collington GK, Trabulsi LR, and Knutton S. Increased levels of  intracellular calcium are not required for the formation of attaching and  effacing lesions by enteropathogenic and enterohemorrhagic Escherichia  coli. Infect Immun 66:  3900\u20133908, 1998.","DOI":"10.1128\/IAI.66.8.3900-3908.1998"},{"key":"REF3","doi-asserted-by":"crossref","unstructured":"Baldwin TJ,  Brooks SF, Knutton S, Manjarrez Hernandez HA, Aitken A, and Williams PH.  Protein phosphorylation by protein kinase C in HEp-2 cells infected with  enteropathogenic Escherichia coli. Infect Immun 58: 761\u2013765,  1990.","DOI":"10.1128\/iai.58.3.761-765.1990"},{"key":"REF4","doi-asserted-by":"crossref","unstructured":"Baldwin TJ,  Ward W, Aitken A, Knutton S, and Williams PH. Elevation of intracellular  free calcium levels in HEp-2 cells infected with enteropathogenic  Escherichia coli. Infect Immun 59: 1599\u20131604,  1991.","DOI":"10.1128\/iai.59.5.1599-1604.1991"},{"key":"REF5","doi-asserted-by":"crossref","unstructured":"Batlle E, Fabre  M, and Garcia de Herreros A. Antipeptide antibodies directed against the  C-terminus of protein kinase C zeta (PKC zeta) react with a  Ca2+- and TPA-sensitive PKC in HT-29 human intestinal  epithelial cells. FEBS Lett 344: 161\u2013165,  1994.","DOI":"10.1016\/0014-5793(94)00379-3"},{"key":"REF6","doi-asserted-by":"crossref","unstructured":"Berra E,  Diaz-Meco MT, Dominguez I, Municio MM, Sanz L, Lozano J, Chapkin RS, and  Moscat J. Protein kinase C zeta isoform is critical for mitogenic signal  transduction. Cell 74:  555\u2013563, 1993.","DOI":"10.1016\/0092-8674(93)80056-K"},{"key":"REF7","doi-asserted-by":"crossref","unstructured":"Berra E,  Diaz-Meco MT, Lozano J, Frutos S, Municio MM, Sanchez P, Sanz L, and Moscat  J. Evidence for a role of MEK and MAPK during signal transduction by  protein kinase C zeta. EMBO J 14: 6157\u20136163,  1995.","DOI":"10.1002\/j.1460-2075.1995.tb00306.x"},{"key":"REF8","doi-asserted-by":"crossref","unstructured":"Bjorkoy G,  Overvatn A, Diaz-Meco MT, Moscat J, and Johansen T. Evidence for a  bifurcation of the mitogenic signaling pathway activated by Ras and  phosphatidylcholine-hydrolyzing phospholipase C. J Biol  Chem 270:  21299\u201321306, 1995.","DOI":"10.1074\/jbc.270.36.21299"},{"key":"REF9","doi-asserted-by":"crossref","unstructured":"Bjorkoy G,  Perander M, Overvatn A, and Johansen T. Reversion of Ras- and  phosphatidylcholine-hydrolyzing phospholipase C-mediated transformation of NIH  3T3 cells by a dominant interfering mutant of protein kinase C lambda is  accompanied by the loss of constitutive nuclear mitogen-activated protein  kinase\/extracellular signal-regulated kinase activity. J Biol  Chem 272:  11557\u201311565, 1997.","DOI":"10.1074\/jbc.272.17.11557"},{"key":"REF10","doi-asserted-by":"crossref","unstructured":"Crane JK and Oh  JS. Activation of host cell protein kinase C by enteropathogenic  Escherichia coli. Infect Immun 65: 3277\u20133285,  1997.","DOI":"10.1128\/iai.65.8.3277-3285.1997"},{"key":"REF11","doi-asserted-by":"crossref","unstructured":"Czerucka D,  Dahan S, Mograbi B, Rossi B, and Rampal P. Implication of  mitogen-activated protein kinases in T84 cell responses to  enteropathogenic Escherichia coli infection. Infect  Immun 69:  1298\u20131305, 2001.","DOI":"10.1128\/IAI.69.3.1298-1305.2001"},{"key":"REF12","doi-asserted-by":"crossref","unstructured":"Diaz-Meco MT,  Berra E, Municio MM, Sanz L, Lozano J, Dominguez I, Diaz-Golpe V, Lain de Lera  MT, Alcami J, and Paya CV. A dominant negative protein kinase C zeta  subspecies blocks NF-kappa B activation. Mol Cell Biol 13: 4770\u20134775,  1993.","DOI":"10.1128\/MCB.13.8.4770"},{"key":"atypb1","doi-asserted-by":"crossref","unstructured":"Diaz-Meco MT,  Dominguez I, Sanz L, Dent P, Lozano J, Municio MM, Berra E, Hay RT, Sturgill  TW, and Moscat J. zeta PKC induces phosphorylation and inactivation of I  kappa B-alpha in vitro. EMBO J 13: 2842\u20132848,  1994.","DOI":"10.1002\/j.1460-2075.1994.tb06578.x"},{"key":"REF14","doi-asserted-by":"crossref","unstructured":"Diaz-Meco MT,  Lozano J, Municio MM, Berra E, Frutos S, Sanz L, and Moscat J. Evidence  for the in vitro and in vivo interaction of Ras with protein kinase C zeta.  J Biol Chem 269:  31706\u201331710, 1994.","DOI":"10.1016\/S0021-9258(18)31753-8"},{"key":"REF15","doi-asserted-by":"crossref","unstructured":"Diaz-Meco MT,  Municio MM, Frutos S, Sanchez P, Lozano J, Sanz L, and Moscat J. The  product of par-4, a gene induced during apoptosis, interacts selectively with  the atypical isoforms of protein kinase C. Cell 86: 777\u2013786,  1996.","DOI":"10.1016\/S0092-8674(00)80152-X"},{"key":"REF16","doi-asserted-by":"crossref","unstructured":"Dominguez I,  Sanz L, Arenzana-Seisdedos F, Diaz-Meco MT, Virelizier JL, and Moscat J.  Inhibition of protein kinase C zeta subspecies blocks the activation of an  NF-kappa B-like activity in Xenopus laevis oocytes. Mol  Cell Biol 13:  1290\u20131295, 1993.","DOI":"10.1128\/MCB.13.2.1290"},{"key":"REF17","doi-asserted-by":"crossref","unstructured":"Folgueira L,  McElhinny JA, Bren GD, MacMorran WS, Diaz-Meco MT, Moscat J, and Paya CV.  Protein kinase C-zeta mediates NF-kappa B activation in human immunodeficiency  virus-infected monocytes. J Virol 70: 223\u2013231,  1996.","DOI":"10.1128\/jvi.70.1.223-231.1996"},{"key":"REF18","doi-asserted-by":"crossref","unstructured":"Gewirtz AT, Rao  AS, Simon PO Jr, Merlin D, Carnes D, Madara JL, and Neish AS. Salmonella typhimurium induces epithelial IL-8 expression via  Ca2+-mediated activation of the NF-kappaB pathway.  J Clin Invest 105:  79\u201392, 2000.","DOI":"10.1172\/JCI8066"},{"key":"REF19","doi-asserted-by":"crossref","unstructured":"Ghosh S and  Baltimore D. Activation in vitro of NF-kappa B by phosphorylation of its  inhibitor I kappa B. Nature 344: 678\u2013682,  1990.","DOI":"10.1038\/344678a0"},{"key":"REF20","doi-asserted-by":"crossref","unstructured":"Guthridge CJ,  Eidlen D, Arend WP, Gutierrez-Hartmann A, and Smith MF Jr.  Lipopolysaccharide and Raf-1 kinase regulate secretory interleukin-1 receptor  antagonist gene expression by mutually antagonistic mechanisms. Mol  Cell Biol 17:  1118\u20131128, 1997.","DOI":"10.1128\/MCB.17.3.1118"},{"key":"REF21","doi-asserted-by":"crossref","unstructured":"Hobbie S, Chen  LM, Davis RJ, and Galan JE. Involvement of mitogen-activated protein  kinase pathways in the nuclear responses and cytokine production induced by  Salmonella typhimurium in cultured intestinal epithelial cells.  J Immunol 159:  5550\u20135559, 1997.","DOI":"10.4049\/jimmunol.159.11.5550"},{"key":"REF22","doi-asserted-by":"crossref","unstructured":"Izumi Y, Hirose  T, Tamai Y, Hirai S, Nagashima Y, Fujimoto T, Tabuse Y, Kemphues KJ, and Ohno  S. An atypical PKC directly associates and colocalizes at the epithelial  tight junction with ASIP, a mammalian homologue of Caenorhabditis  elegans polarity protein PAR-3. J Cell Biol 143: 95\u2013106,  1998.","DOI":"10.1083\/jcb.143.1.95"},{"key":"REF23","doi-asserted-by":"crossref","unstructured":"Keates S,  Keates AC, Warny M, Peek RM Jr, Murray PG, and Kelly CP. Differential  activation of mitogen-activated protein kinases in AGS gastric epithelial  cells by cag+ and cag\u2013 Helicobacter pylori. J  Immunol 163:  5552\u20135559, 1999.","DOI":"10.4049\/jimmunol.163.10.5552"},{"key":"REF24","unstructured":"Koutsouris A,  Savkovic SD, and Hecht G. PKC\u03b6 is activated in intestinal epithelial  cells infected by enteropathogenic E. coli and participates in the  alteration of tight junction (Abstract).  Gastroenterology 122:  A-56, 2002."},{"key":"REF25","doi-asserted-by":"crossref","unstructured":"Lallena MJ,  Diaz-Meco MT, Bren G, Paya CV, and Moscat J. Activation of IkappaB kinase  beta by protein kinase C isoforms. Mol Cell Biol 19: 2180\u20132188,  1999.","DOI":"10.1128\/MCB.19.3.2180"},{"key":"REF26","doi-asserted-by":"crossref","unstructured":"Lee JC, Laydon  JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ,  Heys JR, and Landvatter SW. A protein kinase involved in the regulation of  inflammatory cytokine biosynthesis. Nature 372: 739\u2013746,  1994.","DOI":"10.1038\/372739a0"},{"key":"REF27","doi-asserted-by":"crossref","unstructured":"Li JD, Feng W,  Gallup M, Kim JH, Gum J, Kim Y, and Basbaum C. Activation of NF-kappaB via  a Src-dependent Ras-MAPK-pp90rsk pathway is required for Pseudomonas  aeruginosa-induced mucin overproduction in epithelial cells.  Proc Natl Acad Sci USA 95:  5718\u20135723, 1998.","DOI":"10.1073\/pnas.95.10.5718"},{"key":"REF28","doi-asserted-by":"crossref","unstructured":"Liao DF, Monia  B, Dean N, and Berk BC. Protein kinase C-zeta mediates angiotensin II  activation of ERK1\/2 in vascular smooth muscle cells. J Biol  Chem 272:  6146\u20136150, 1997.","DOI":"10.1074\/jbc.272.10.6146"},{"key":"REF29","doi-asserted-by":"crossref","unstructured":"Ling L, Cao Z,  and Goeddel DV. NF-kappaB-inducing kinase activates IKK-alpha by  phosphorylation of Ser-176. Proc Natl Acad Sci USA 95: 3792\u20133797,  1998.","DOI":"10.1073\/pnas.95.7.3792"},{"key":"REF30","doi-asserted-by":"crossref","unstructured":"Lozano J, Berra  E, Municio MM, Diaz-Meco MT, Dominguez I, Sanz L, and Moscat J. Protein  kinase C zeta isoform is critical for kappa B-dependent promoter activation by  sphingomyelinase. J Biol Chem 269: 19200\u201319202,  1994.","DOI":"10.1016\/S0021-9258(17)32152-X"},{"key":"REF31","doi-asserted-by":"crossref","unstructured":"Madara JL,  Stafford J, Dharmsathaphorn K, and Carlson S. Structural analysis of a  human intestinal epithelial cell line.  Gastroenterology 92:  1133\u20131145, 1987.","DOI":"10.1016\/S0016-5085(87)91069-9"},{"key":"REF32","doi-asserted-by":"crossref","unstructured":"Malinin NL,  Boldin MP, Kovalenko AV, and Wallach D. MAP3K-related kinase involved in  NF-kappaB induction by TNF, CD95 and IL-1. Nature 385: 540\u2013544,  1997.","DOI":"10.1038\/385540a0"},{"key":"REF33","doi-asserted-by":"crossref","unstructured":"Martin AG,  San-Antonio B, and Fresno M. Regulation of nuclear factor kappa B  transactivation. Implication of phosphatidylinositol 3-kinase and protein  kinase C zeta in c-Rel activation by tumor necrosis factor alpha. J  Biol Chem 276:  15840\u201315849, 2001.","DOI":"10.1074\/jbc.M011313200"},{"key":"REF34","doi-asserted-by":"crossref","unstructured":"Mercurio F, Zhu  H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M,  Manning A, and Rao A. IKK-1 and IKK-2: cytokine-activated IkappaB kinases  essential for NF-kappaB activation. Science 278: 860\u2013866,  1997.","DOI":"10.1126\/science.278.5339.860"},{"key":"REF35","doi-asserted-by":"crossref","unstructured":"Monick MM,  Carter AB, Flaherty DM, Peterson MW, and Hunninghake GW. Protein kinase C  zeta plays a central role in activation of the p42\/44 mitogen-activated  protein kinase by endotoxin in alveolar macrophages. J  Immunol 165:  4632\u20134639, 2000.","DOI":"10.4049\/jimmunol.165.8.4632"},{"key":"REF36","doi-asserted-by":"crossref","unstructured":"Monick MM,  Carter AB, Gudmundsson G, Mallampalli R, Powers LS, and Hunninghake GW. A  phosphatidylcholine-specific phospholipase C regulates activation of p42\/44  mitogen-activated protein kinases in lipopolysaccharide-stimulated human  alveolar macrophages. J Immunol 162: 3005\u20133012,  1999.","DOI":"10.4049\/jimmunol.162.5.3005"},{"key":"REF37","doi-asserted-by":"crossref","unstructured":"Moscat J and  Diaz-Meco MT. The atypical protein kinase Cs. Functional specificity  mediated by specific protein adapters. EMBO Rep 1: 399\u2013403,  2000.","DOI":"10.1093\/embo-reports\/kvd098"},{"key":"REF38","doi-asserted-by":"crossref","unstructured":"Nakano H,  Shindo M, Sakon S, Nishinaka S, Mihara M, Yagita H, and Okumura K.  Differential regulation of IkappaB kinase alpha and beta by two upstream  kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase\/ERK  kinase kinase-1. Proc Natl Acad Sci USA 95: 3537\u20133542,  1998.","DOI":"10.1073\/pnas.95.7.3537"},{"key":"REF39","doi-asserted-by":"crossref","unstructured":"Nusrat A, Chen  JA, Foley CS, Liang TW, Tom J, Cromwell M, Quan C, and Mrsny RJ. The  coiled-coil domain of occludin can act to organize structural and functional  elements of the epithelial tight junction. J Biol Chem 275: 29816\u201329822,  2000.","DOI":"10.1074\/jbc.M002450200"},{"key":"REF40","doi-asserted-by":"crossref","unstructured":"Procyk KJ,  Rippo MR, Testi R, Hoffmann F, Parker PJ, and Baccarini M. Distinct  mechanisms target stress and extracellular signal-activated kinase 1 and Jun  N-terminal kinase during infection of macrophages with Salmonella.  J Immunol 163:  4924\u20134930, 1999.","DOI":"10.4049\/jimmunol.163.9.4924"},{"key":"REF41","doi-asserted-by":"crossref","unstructured":"Rahman A, Anwar  KN, and Malik AB. Protein kinase C-\u03b6 mediates TNF-\u03b1-induced  ICAM-1 gene transcription in endothelial cells. Am J Physiol Cell  Physiol 279:  C906\u2013C914, 2000.","DOI":"10.1152\/ajpcell.2000.279.4.C906"},{"key":"REF42","doi-asserted-by":"crossref","unstructured":"Regnier CH,  Song HY, Gao X, Goeddel DV, Cao Z, and Rothe M. Identification and  characterization of an IkappaB kinase. Cell 90: 373\u2013383,  1997.","DOI":"10.1016\/S0092-8674(00)80344-X"},{"key":"REF43","doi-asserted-by":"crossref","unstructured":"Rust C, Karnitz  LM, Paya CV, Moscat J, Simari RD, and Gores GJ. The bile acid  taurochenodeoxycholate activates a phosphatidylinositol 3-kinase-dependent  survival signaling cascade. J Biol Chem 275: 20210\u201320216,  2000.","DOI":"10.1074\/jbc.M909992199"},{"key":"REF44","doi-asserted-by":"crossref","unstructured":"Sajan MP,  Standaert ML, Bandyopadhyay G, Quon MJ, Burke TR Jr, and Farese RV.  Protein kinase C-zeta and phosphoinositide-dependent protein kinase-1 are  required for insulin-induced activation of ERK in rat adipocytes. J  Biol Chem 274:  30495\u201330500, 1999.","DOI":"10.1074\/jbc.274.43.30495"},{"key":"REF45","doi-asserted-by":"crossref","unstructured":"Sakurai H,  Chiba H, Miyoshi H, Sugita T, and Toriumi W. I\u03baB kinases  phosphorylate NF-\u03baB p65 subunit on serine 536 in the transactivation  domain. J Biol Chem 274:  30353\u201330356, 1999.","DOI":"10.1074\/jbc.274.43.30353"},{"key":"REF46","doi-asserted-by":"crossref","unstructured":"Savkovic S,  Koutsouris A, Wu G, and Hecht G. Infection of intestinal epithelial cells  with bacterial pathogens decreases luciferase activity: ramifications for  reporter gene studies. Biotechniques 29: 514\u2013522,  2000.","DOI":"10.2144\/00293st03"},{"key":"REF47","unstructured":"Savkovic S,  Koutsouris A, and Hecht G. Activation of NF-\u03baB and IL-8 gene  expression in response to enteropathogenic E. coli infection involves  reactive oxygen intermediates and protein kinases (Abstract).  Gastroenterology 112:  A401, 1997."},{"key":"REF48","doi-asserted-by":"crossref","unstructured":"Savkovic S,  Koutsouris A, and Hecht G. Activation of NF-\u03baB in intestinal  epithelial cells by enteropathogenic Escherichia coli. Am J Physiol  Cell Physiol 273:  C1160\u2013C1167, 1997.","DOI":"10.1152\/ajpcell.1997.273.4.C1160"},{"key":"REF49","doi-asserted-by":"crossref","unstructured":"Savkovic SD,  Koutsouris A, and Hecht G. Attachment of a non-invasive enteric pathogen,  enteropathogenic Escherichia coli, to cultured human intestinal  epithelial monolayers induces transmigration of neutrophils. Infect  Immun 64:  4480\u20134487, 1996.","DOI":"10.1128\/iai.64.11.4480-4487.1996"},{"key":"REF50","doi-asserted-by":"crossref","unstructured":"Savkovic SD,  Ramaswamy A, Koutsouris A, and Hecht G. EPEC-activated ERK1\/2 participate  in inflammatory response but not tight junction barrier disruption.  Am J Physiol Gastrointest Liver Physiol 281: G890\u2013G898,  2001.","DOI":"10.1152\/ajpgi.2001.281.4.G890"},{"key":"REF51","doi-asserted-by":"crossref","unstructured":"Schmid RM and  Adler G. NF-kappaB\/Rel\/IkappaB: implications in gastrointestinal diseases.  Gastroenterology 118:  1208\u20131228, 2000.","DOI":"10.1016\/S0016-5085(00)70374-X"},{"key":"REF52","doi-asserted-by":"crossref","unstructured":"Schonwasser DC,  Marais RM, Marshall CJ, and Parker PJ. Activation of the mitogen-activated  protein kinase\/extracellular signal-regulated kinase pathway by conventional,  novel, and atypical protein kinase C isotypes. Mol Cell  Biol 18:  790\u2013798, 1998.","DOI":"10.1128\/MCB.18.2.790"},{"key":"REF53","doi-asserted-by":"crossref","unstructured":"Schouten GJ,  Vertegaal AC, Whiteside ST, Israel A, Toebes M, Dorsman JC, van der Eb AJ, and  Zantema A. IkappaB alpha is a target for the mitogen-activated 90 kDa  ribosomal S6 kinase. EMBO J 16:  3133\u20133144, 1997.","DOI":"10.1093\/emboj\/16.11.3133"},{"key":"REF54","doi-asserted-by":"crossref","unstructured":"Simonovic I,  Rosenberg J, Koutsouris A, and Hecht G. Enteropathogenic Escherichia  coli dephosphorylates and dissociates occludin from intestinal epithelial  tight junctions. Cell Microbiol 2: 305\u2013315,  2000.","DOI":"10.1046\/j.1462-5822.2000.00055.x"},{"key":"REF55","doi-asserted-by":"crossref","unstructured":"Soltoff SP.  Rottlerin is a mitochondrial uncoupler that decreases cellular ATP levels and  indirectly blocks protein kinase Cdelta tyrosine phosphorylation. J  Biol Chem 276:  37986\u201337992, 2001.","DOI":"10.1074\/jbc.M105073200"},{"key":"REF56","doi-asserted-by":"crossref","unstructured":"Sontag E,  Sontag JM, and Garcia A. Protein phosphatase 2A is a critical regulator of  protein kinase C zeta signaling targeted by SV40 small t to promote cell  growth and NF-kappaB activation. EMBO J 16: 5662\u20135671,  1997.","DOI":"10.1093\/emboj\/16.18.5662"},{"key":"REF57","doi-asserted-by":"crossref","unstructured":"Stuart RO and  Nigam SK. Regulated assembly of tight junctions by protein kinase C.  Proc Natl Acad Sci USA 92:  6072\u20136076, 1995.","DOI":"10.1073\/pnas.92.13.6072"},{"key":"REF58","doi-asserted-by":"crossref","unstructured":"Tando Y, Algul  H, Wagner M, Weidenbach H, Adler G, and Schmid RM. Caerulein-induced  NF-\u03baB\/Rel activation requires both Ca2+ and  protein kinase C as messengers. Am J Physiol Gastrointest Liver  Physiol 277:  G678\u2013G686, 1999.","DOI":"10.1152\/ajpgi.1999.277.3.G678"},{"key":"REF59","doi-asserted-by":"crossref","unstructured":"Vanden BW,  Plaisance S, Boone B, De Bosscher MK, Schmitz L, Fiers W, and Haegeman  G. p38 and extracellular signal-regulated kinase mitogen-activated protein  kinase pathways are required for nuclear factor-B p65 transactivation mediated  by tumor necrosis factor. J Biol Chem 273: 3285\u20133290,  1998.","DOI":"10.1074\/jbc.273.6.3285"},{"key":"REF60","doi-asserted-by":"crossref","unstructured":"Verma IM and  Stevenson J. IkappaB kinase: beginning, not the end. Proc Natl  Acad Sci USA 94:  11758\u201311760, 1997.","DOI":"10.1073\/pnas.94.22.11758"},{"key":"REF61","doi-asserted-by":"crossref","unstructured":"Warny M, Keates  AC, Keates S, Castagliuolo I, Zacks JK, Aboudola S, Qamar A,  Pothoulakis C, LaMont JT, and Kelly CP. p38 MAP kinase activation by  Clostridium difficile toxin A mediates monocyte necrosis, IL-8  production, and enteritis. J Clin Invest 105: 1147\u20131156,  2000.","DOI":"10.1172\/JCI7545"},{"key":"REF62","doi-asserted-by":"crossref","unstructured":"Widmann C,  Gibson M, Jarpe B, and Johnson L. Mitogen-activated protein kinase:  conservation of a three-kinase module from yeast to human. Physiol  Rev 79:  143\u2013180, 1999.","DOI":"10.1152\/physrev.1999.79.1.143"},{"key":"REF63","doi-asserted-by":"crossref","unstructured":"Woronicz JD,  Gao X, Cao Z, Rothe M, and Goeddel DV. IkappaB kinase-beta: NF-kappaB  activation and complex formation with IkappaB kinase-alpha and NIK.  Science 278:  866\u2013869, 1997.","DOI":"10.1126\/science.278.5339.866"},{"key":"REF64","doi-asserted-by":"crossref","unstructured":"Zabel U and  Baeuerle PA. Purified human I kappa B can rapidly dissociate the complex  of the NF-kappa B transcription factor with its cognate DNA.  Cell 61:  255\u2013265, 1990.","DOI":"10.1016\/0092-8674(90)90806-P"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00444.2002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:03:15Z","timestamp":1718650995000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00444.2002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9]]},"references-count":64,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,9]]}},"alternative-id":["10.1152\/ajpcell.00444.2002"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00444.2002","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9]]}}}