The article provides a comprehensive overview of the JAK-STAT signaling pathway, which is crucial for cytokine-induced gene expression. It begins by tracing the historical development of interferons (IFNs) and other cytokines, highlighting the identification of the JAK-STAT signaling paradigm. The review then delves into the structure and function of JAKs (Janus kinases) and STATs (signal transducer and activator of transcription proteins). JAKs, including Jak1, Jak2, Jak3, and Tyk2, are tyrosine kinases that play a central role in cytokine signaling. They are activated upon ligand binding, leading to the phosphorylation of specific tyrosine residues on cytokine receptors. This activation recruits STAT proteins, which are inactive homodimers in resting cells. Activated STATs undergo dimerization, translocate to the nucleus, and bind to specific DNA sequences to activate gene transcription. The STAT family consists of seven members (STAT1-6 and Stat7), each with distinct functions and roles in various cytokine responses. For example, Stat1 is essential for the response to IFNs and IL-12, while Stat3 is involved in IL-6 and IL-10 signaling. STATs can be modified by phosphorylation, acetylation, and O-glycosylation, which influence their activity and stability. The article also discusses the regulation of STAT activity, including dephosphorylation, nuclear import and export, and feedback inhibition by SOCS proteins. Additionally, it explores the recruitment of chromatin-modifying enzymes and coactivators by STATs, which contribute to their transcriptional activation. Overall, the JAK-STAT signaling pathway is a highly regulated process that mediates the biological responses to cytokines, with implications in both normal and pathological conditions.The article provides a comprehensive overview of the JAK-STAT signaling pathway, which is crucial for cytokine-induced gene expression. It begins by tracing the historical development of interferons (IFNs) and other cytokines, highlighting the identification of the JAK-STAT signaling paradigm. The review then delves into the structure and function of JAKs (Janus kinases) and STATs (signal transducer and activator of transcription proteins). JAKs, including Jak1, Jak2, Jak3, and Tyk2, are tyrosine kinases that play a central role in cytokine signaling. They are activated upon ligand binding, leading to the phosphorylation of specific tyrosine residues on cytokine receptors. This activation recruits STAT proteins, which are inactive homodimers in resting cells. Activated STATs undergo dimerization, translocate to the nucleus, and bind to specific DNA sequences to activate gene transcription. The STAT family consists of seven members (STAT1-6 and Stat7), each with distinct functions and roles in various cytokine responses. For example, Stat1 is essential for the response to IFNs and IL-12, while Stat3 is involved in IL-6 and IL-10 signaling. STATs can be modified by phosphorylation, acetylation, and O-glycosylation, which influence their activity and stability. The article also discusses the regulation of STAT activity, including dephosphorylation, nuclear import and export, and feedback inhibition by SOCS proteins. Additionally, it explores the recruitment of chromatin-modifying enzymes and coactivators by STATs, which contribute to their transcriptional activation. Overall, the JAK-STAT signaling pathway is a highly regulated process that mediates the biological responses to cytokines, with implications in both normal and pathological conditions.