title: Synergistic activation of NF-kappa B by functional cooperation between vav and PKCtheta in T lymphocytes.
abstract: Here we identified PKCtheta as an activator of transcription factor NF-kappaB in T cells. PKCtheta-induced NF-kappaB activation was synergistically augmented by Vav. Several experimental approaches revealed that PKCtheta is located downstream from Vav in the control of the pathway leading to synergistic NF-kappaB activation. In addition to the synergistic activation cascade, Vav also triggered NF-kappaB activity on a separate route. CD3/CD28-induced activation of NF-kappaB was inhibited by dominant negative forms of Vav or PKCtheta, revealing their essential role in this activation pathway. The Vav/PKCtheta-mediated signals preferentially activated IkappaB kinase beta. Vav and PKCtheta were found to be constitutively associated in unstimulated T cells. Only the ligation of the costimulatory CD28 receptor, but not of the T cell receptor, resulted in the transient dissociation of the Vav-PKCtheta complex. In contrast, T cell receptor/CD28 costimulation resulted in faster dissociation and slower reassociation kinetics.
authors.affiliation: German Cancer Research Center, Department of Immunochemistry (G0200), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Dienz
authors.forename: S P
authors.initials: SP
authors.lastname: Hehner
authors.forename: W
authors.initials: W
authors.lastname: Droge
authors.forename: M L
authors.initials: ML
authors.lastname: Schmitz
mesh_terms: D015703:Antigens, CD / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D018797:Cell Cycle Proteins; D006801:Humans; D051550:I-kappa B Kinase; D007527:Isoenzymes / Q000378:metabolism*; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D018797:Cell Cycle Proteins; D007527:Isoenzymes; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011994:Recombinant Proteins; C496618:VAV1 protein, human; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D001616:beta-Galactosidase