Homotrimeric TNF superfamily (TNFSF) ligands signal by inducing trimerization or higher order oligomerization of their cognate receptors. Upon binding its trivalent ligands lymphotoxin and LIGHT (TNFSF14), lymphotoxin-beta receptor (LTBR/TNFR3) undergoes ordered aggregation or clustering. Heterotrimeric lymphotoxin alpha1beta2 (LTA1B2) induces dimerization rather than trimerization of the LTBR. The crystal structure of this complex reveals that dimerization of LTBA is necessary and sufficient for signal transduction (Sudhamsu et al. 2013). Upon oligomerization, LTBR activates multiple signaling pathways including transcriptional factor NF kappa B (NF-kB), c-Jun N-terminal kinase (JNK), and cell death.
Hymowitz, SG, Grogan, JL, Chiang, EY, Sudhamsu, J, Yin, J, Starovasnik, MA
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