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Publication : Induction of the alternative NF-κB pathway by lymphotoxin αβ (LTαβ) relies on internalization of LTβ receptor.

First Author  Ganeff C Year  2011
Journal  Mol Cell Biol Volume  31
Issue  21 Pages  4319-34
PubMed ID  21896778 Mgi Jnum  J:178327
Mgi Id  MGI:5298150 Doi  10.1128/MCB.05033-11
Citation  Ganeff C, et al. (2011) Induction of the alternative NF-kappaB pathway by lymphotoxin alphabeta (LTalphabeta) relies on internalization of LTbeta receptor. Mol Cell Biol 31(21):4319-34
abstractText  Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-kappaB pathways. However, how a single receptor engages these two distinct pathways is still poorly understood. Using lymphotoxin beta receptor (LTbetaR) as a prototype, we showed that activation of the alternative, but not the classical, NF-kappaB pathway relied on internalization of the receptor. Further molecular analyses revealed a specific cytosolic region of LTbetaR essential for its internalization, TRAF3 recruitment, and p100 processing. Interestingly, we found that dynamin-dependent, but clathrin-independent, internalization of LTbetaR appeared to be required for the activation of the alternative, but not the classical, NF-kappaB pathway. In vivo, ligand-induced internalization of LTbetaR in mesenteric lymph node stromal cells correlated with induction of alternative NF-kappaB target genes. Thus, our data shed light on LTbetaR cellular trafficking as a process required for specific biological functions of NF-kappaB.
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