Cytokine and NF-κB Signaling
Cytokine and NF-κB signaling pathways are intricately linked biochemical cascades that are involved in the innate and adaptive immune response, inflammation and stress responses.
Proinflammatory cytokines, such as IFNγ and TNFα, activate the IKK complex, which phosphorylates IκB and targets it for proteasomal degradation. This frees NF-κB and, after phosphorylation, allows it to translocate to the nucleus. In the nucleus NF-κB acts alone, or with other transcription factors such as AP-1 and STAT, to induce target gene expression.
In addition to activation by cytokines, this pathway can be activated by cellular stresses such as UV light and ischemia. JNK (also known as stress-activated protein kinase) activates NF-κB and allows target gene expression. Similarly, JAK, which is associated with cytokine receptors, phosphorylates STAT and enhances NF-κB-STAT-mediated gene expression.