STATs (Signal-Transducing Activators of Transcription) are the principle substrates of JAK kinases, and mediators of cytokine signaling. STAT proteins have SH2 domains, and once phosphorylated by JAK kinases, STATs dimerize in a head-to-tail fashion, through their SH2 domains. STAT1 is a critical mediator of IFN signaling, STAT4 is specific to IL-12, STAT6 is activated primarily by IL-4 and IL-13, while STAT5 A and B appear to be most important to the function of growth hormone and prolactin. STAT3 is involved in multiple signaling pathways, and mice deficient in it are not viable. In addition to tyrosine phosphorylation, many STAT proteins are targets of Ser/Thr kinases, and those phosphorylation events potentiate STAT-induced transcription. The phosphorylation state of STATs can be monitored by phosphorylation state-specific antibodies.