The JAK-STAT Pathway: Impact on Human Disease and Therapeutic Intervention

Abstract

The Janus kinase (JAK), signal transducer of activation (STAT) pathway, discovered by investigating interferon gene induction, is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules. This pathway provides an elegant, and remarkably straightforward mechanism whereby extracellular factors control gene expression. It thus serves as a fundamental paradigm for how cells sense environmental cues and interpret these signals to regulate cell growth and differentiation. Functionally relevant genetic mutations and polymorphisms are relevant to a variety of human diseases, especially cancer and immune-related conditions. Finally, the clinical relevance of the pathway has been confirmed by the emergence of a new class of therapeutics that target JAKs.