Molecular structure and function of janus kinases: Implications for the development of inhibitors

Abstract

Cytokines can trigger multiple signalling pathways, including Janus tyrosine kinases [JAK] and signal transducers and activators of transcription [STATS] pathways. JAKs are cytoplasmic proteins that, following the binding of cytokines to their receptors, transduce the signal by phosphorylating STAT proteins which enter the nuclei and rapidly target gene promoters to regulate gene transcription. Due to the critical involvement of JAK proteins in mediating innate and adaptive immune responses, these family of kinases have become desirable pharmacological targets in inflammatory diseases, including ulcerative colitis and Crohn's disease. In this review we provide an overview of the main cytokines that signal through the JAK/STAT pathway and the available in vivo evidence on mutant or deleted JAK proteins, and discuss the implications of pharmacologically targeting this kinase family in the context of inflammatory diseases.