Category: signaling
Cytokine receptor → JAK → STAT → nuclear → transcription. Cytokine binding triggers receptor dimerization → JAK (1/2/3/TYK2) cross-phosphorylation → JAK phosphorylates the receptor cytoplasmic tail → STAT (1-6) recruited via SH2 → STAT phosphorylated → dimerizes → nuclear translocation → DNA binding → gene transcription. Receptor-JAK pairings: IFN-γ → JAK1/2 → STAT1; IL-6 family → JAK1/TYK2 → STAT3; IL-2/4/7/9/15/21 → JAK1/3 → STAT5/6; thrombopoietin/erythropoietin → JAK2 → STAT5. JAK INHIBITORS: tofacitinib (JAK1/3), baricitinib (JAK1/2), upadacitinib (JAK1-selective), ruxolitinib (JAK1/2 — myelofibrosis, PV, GVHD), fedratinib (JAK2). Class warning: MACE / VTE / malignancy (ORAL Surveillance trial).