Cytokine Signaling Pathways

Cytokine signaling involves binding of extracellular cytokines to specific membrane receptors, triggering intracellular signal transduction cascades that alter gene expression. The JAK-STAT pathway is the primary signaling mechanism for Type I and II cytokine receptors: cytokine binding activates receptor-associated Janus kinases (JAK1, JAK2, JAK3, TYK2), which phosphorylate STAT proteins; phosphorylated STATs dimerize, translocate to the nucleus, and activate target gene transcription (immune cell differentiation, proliferation, survival). The NF-κB pathway mediates TNF-alpha, IL-1, and TLR signaling: activating IKK which phosphorylates IκB, releasing NF-κB to translocate to the nucleus and activate pro-inflammatory gene transcription. These pathways are now therapeutic targets: JAK inhibitors (tofacitinib, baricitinib, ruxolitinib) and anti-TNF biologics (infliximab, adalimumab) specifically target these cascades.