The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways.
The lymphotoxin-beta receptor (LTbetaR) plays critical roles in inflammation and lymphoid organogenesis through activation of NF-kappaB. In addition to activation of the classical NF-kappaB, ligation of this receptor induces the processing of the cytosolic NF-kappaB2/p100 precursor to yield the mature p52 subunit, followed by translocation of p52 to the nucleus. This activation of NF-kappaB2 requires NIK and IKKalpha, while NEMO/IKKgamma is dispensable for p100 processing. IKKbeta-dependent activation of canonical NF-kappaB is required for the expression but not processing of p100 and for the expression of proinflammatory molecules including VCAM-1, MIP-1beta, and MIP-2 in response to LTbetaR ligation. In contrast, IKKalpha controls the induction by LTbetaR ligation of chemokines and cytokines involved in lymphoid organogenesis, including SLC, BLC, ELC, SDF1, and BAFF.
Dejardin
Emmanuel
E
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Droin
Nathalie M
NM
Delhase
Mireille
M
Haas
Elvira
E
Cao
Yixue
Y
Makris
Constantin
C
Li
Zhi-Wei
ZW
Karin
Michael
M
Ware
Carl F
CF
Green
Douglas R
DR
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase; D053259:Lymphotoxin beta Receptor; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
D051550:I-kappa B Kinase; D053259:Lymphotoxin beta Receptor; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D017346:Protein Serine-Threonine Kinases; D018124:Receptors, Tumor Necrosis Factor; D000097782:NF-kappaB-Inducing Kinase; C505697:LTBR protein, human; C505699:Ltbr protein, mouse; C496559:CHUK protein, human; C496564:Chuk protein, mouse; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse