The JAK-STAT signaling pathway is initiated by the binding of an extracellular ligand to a cell surface receptor leading to receptor dimerization and the intracellular activation of a Janus kinase (JAK) family member. JAK phosphorylates cytoplasmic STAT family members which dimerize, translocate into the nucleus and regulate target gene expression. In Drosophila, the core pathway is limited to three ligands (the Unpaired family of cytokines), a single receptor (dome), JAK kinase (hop) and STAT (Stat92E). (Adapted from FBrf0225259).