Overview
Clinical Meaning
Cytokine signaling involves binding of extracellular cytokines to specific membrane receptors, triggering intracellular signal transduction cascades that alter gene expression.
WHNP
WHNP
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.
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