Figure 2.

The LTβR signaling pathway in lymphatic endothelial cell (LEC). LTα1β2 engagement of LTβR initiates the recruitment of TRAF2 and TRAF3 to the LTβR complex, where TRAF2 and TRAF3 are degraded by cIAP1/2, and result in NF-κB-inducing kinase (NIK) stabilization and accumulation. NIK complexed with IKKα is activated and leads to the homodimeric IKKα phosphorylation. Eventually, the p100 precursor binding with RelB is cleaved to p52 and causes RelB-p52 heterodimeric complex translocation to the nucleus to initiate chemokine gene transcription. LTβR ligation also activates IKKα/β phosphorylation and RelA/p50 nuclear translocation, which leads to gene transcription of inflammatory and cell adhesion molecules. TRAF-2-mediated K63 ubiquitination of cIAP1/2 is also linked to the activation of canonical NFκB pathway.