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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1048-1055. Prepublished online as a Blood First Edition Paper on September 29, 2005; DOI 10.1182/blood-2005-06-2452. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-06-2452v1 107/3/1048    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lo, J. C. Articles by Fu, Y.-X. Search for Related Content PubMed PubMed Citation Articles by Lo, J. C. Articles by Fu, Y.-X. Related Collections Hematopoiesis and Stem Cells Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Coordination between NF-B family members p50 and p52 is essential for mediating LTR signals in the development and organization of secondary lymphoid tissues James C. Lo, Soumen Basak, Ethan S. James, Raechel S. Quiambo, Marcus C. Kinsella, Maria-Luisa Alegre, Falk Weih, Guido Franzoso, Alexander Hoffmann, and Yang-Xin Fu From the Committee on Immunology and Department of Pathology, The University of Chicago, IL; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA; and Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, Karlsruhe, Germany. Recent studies revealed that the lymphotoxin/lymphotoxin beta receptor (LT)/LTR system activates the noncanonical nuclear factor-B (NF-B) signaling pathway involving I kappa B kinase 1/I kappa B kinase (IKK1/IKK) and NF-B-inducing kinase (NIK) to direct processing of the nfb2 protein p100 to yield RelB:p52 complexes. Despite the biochemical evidence, LT-, RelB-, p52-deficient mice show discrepant phenotypes. We now demonstrate that p105/p50 also constitutes an important pathway for LTR signaling. Our studies revealed that mice deficient in either p50 or p52 have defects in the formation of inguinal lymph nodes (LNs), but that the complete defect in lymph node formation and splenic microarchitecture seen in LT-deficient mice is recapitulated only in mice deficient in both p50 and p52. Biochemically, we find not only that both p50- and p52-containing NF-B activities are induced by LTR signaling, but that the induction of NF-B-containing complexes by LTR engagement is perturbed in single knockouts. Importantly, the LTR can additionally activate the less well-characterized p52:RelA and p50:RelB pathways, which play pivotal roles in vivo for the development and organization of lymphoid structures. Our genetic, cellular, and molecular evidence points toward a model of LT-mediated NF-B regulation in which p105/p50 and p100/p52 have distinct and coordinating molecular specificities but differ in the upstream signaling pathways that regulate them. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Basak, V. F.-S. Shih, and A. Hoffmann Generation and Activation of Multiple Dimeric Transcription Factors within the NF-{kappa}B Signaling System Mol. Cell. Biol., May 15, 2008; 28(10): 3139 - 3150. [Abstract] [Full Text] [PDF] E. Tucker, K. O'Donnell, M. Fuchsberger, A. A. Hilton, D. Metcalf, K. Greig, N. A. Sims, J. M. Quinn, W. S. Alexander, D. J. Hilton, et al. A Novel Mutation in the Nfkb2 Gene Generates an NF-{kappa}B2 "Super Repressor" J. Immunol., December 1, 2007; 179(11): 7514 - 7522. [Abstract] [Full Text] [PDF] A. White, D. Carragher, S. Parnell, A. Msaki, N. Perkins, P. Lane, E. Jenkinson, G. Anderson, and J. H. Caamano Lymphotoxin a-dependent and -independent signals regulate stromal organizer cell homeostasis during lymph node organogenesis Blood, September 15, 2007; 110(6): 1950 - 1959. [Abstract] [Full Text] [PDF] W. Kang, K. A. Kudsk, Y. Sano, J. Lan, F. Yang-Xin, F. E. Gomez, and Y. Maeshima Effects of Lymphotoxin {beta} Receptor Blockade on Intestinal Mucosal Immunity JPEN J Parenter Enteral Nutr, September 1, 2007; 31(5): 358 - 365. [Abstract] [Full Text] [PDF] R. T. Taylor, S. R. Patel, E. Lin, B. R. Butler, J. G. Lake, R. D. Newberry, and I. R. Williams Lymphotoxin-Independent Expression of TNF-Related Activation-Induced Cytokine by Stromal Cells in Cryptopatches, Isolated Lymphoid Follicles, and Peyer's Patches J. Immunol., May 1, 2007; 178(9): 5659 - 5667. [Abstract] [Full Text] [PDF] F. Moore, S. Buonocore, E. Aksoy, N. Ouled-Haddou, S. Goriely, E. Lazarova, F. Paulart, C. Heirman, E. Vaeremans, K. Thielemans, et al. An Alternative Pathway of NF-{kappa}B Activation Results in Maturation and T Cell Priming Activity of Dendritic Cells Overexpressing a Mutated I{kappa}B{alpha} J. Immunol., February 1, 2007; 178(3): 1301 - 1311. [Abstract] [Full Text] [PDF] J. Zhang, M. A. Warren, S. F. Shoemaker, and M. M. Ip NF{kappa}B1/p50 Is Not Required for Tumor Necrosis Factor-Stimulated Growth of Primary Mammary Epithelial Cells: Implications for NF{kappa}B2/p52 and RelB Endocrinology, January 1, 2007; 148(1): 268 - 278. [Abstract] [Full Text] [PDF] C. Wietek, C. S. Cleaver, V. Ludbrook, J. Wilde, J. White, D. J. Bell, M. Lee, M. Dickson, K. P. Ray, and L. A. J. O'Neill I{kappa}B Kinase {epsilon} Interacts with p52 and Promotes Transactivation via p65 J. Biol. Chem., November 17, 2006; 281(46): 34973 - 34981. [Abstract] [Full Text] [PDF]

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