An overview of cytokine signaling. Cytokines bind to homodimeric or heterodimeric receptors, which are constitutively bound to Jaks. Jaks are thought to be activated by a conformational change in the receptor that allows trans- and/or auto-phosphorylation of the two bound Jaks. These in turn phosphorylate the cytokine receptors. Stat proteins bind the phosphorylated receptor chains, allowing the Jaks to phosphorylate the Stats. Phosphorylated Stats form dimers and translocate and accumulate in the nucleus, where they regulate gene expression.