LPS induction of the TF gene in monocytes.

Binding of LPS to the CD14 and TLR4/MD2 complex activates several intracellular signaling pathways that include ERK1/2, JNK, and NF-κB. The ERK1/2 pathway rapidly phosphorylates Elk-1 in an Elk-1/SRF complex that is bound to the Egr-1 promoter. We propose that newly synthesized Egr-1 binds to the TF promoter and, in association with AP-1 and c-Rel/p65, induces TF gene expression. JNK phosphorylates and activates AP-1 proteins. IKKβ phosphorylates inhibitor proteins, which allows nuclear translocation of c-Rel/p65. E indicates Egr-1; F, c-Fos; I, IκBs; J, c-Jun; R, c-Rel; 65, p65.