Getting the message across, STAT! Design principles of a molecular signaling circuit

The STAT transcription factors, usually referred to as “latent cytoplasmic proteins,” have experienced a fundamental reevaluation of their dynamic properties. This review focuses on recent studies that have identified continuous transport factor–independent nucleocytoplasmic cycling of STAT1, STAT3, and STAT5 as a basic principle of cytokine signaling. In addition, molecular mechanisms that modulate flux rates or cause retention were recognized, and together these findings have provided novel insight into the rules of cellular signal processing.