Biology and significance of the JAK/STAT signalling pathways

Abstract

Since its discovery two decades ago, the activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway by numerous cytokines and growth factors has resulted in it becoming one of the most well-studied intracellular signalling networks. The field has progressed from the identification of the individual components to high-resolution crystal structures of both JAK and STAT, and an understanding of the complexities of the molecular activation and deactivation cycle which results in a diverse, yet highly specific and regulated pattern of transcriptional responses. While there is still more to learn, we now appreciate how disruption and deregulation of this pathway can result in clinical disease and look forward to adoption of the next generation of JAK inhibitors in routine clinical treatment.

Keywords::

• JAK
• STAT
• signalling
• cytokine
• receptor
• SOCS

Acknowledgements

There have been many papers published in the past 20 years that have contributed to our understanding of the JAK/STAT pathway. Due to space constraints and in the interests of clarity, we have been unable to cite all relevant references. We apologise to the authors of those papers that have not been included and do not mean to infer that their contribution has been of any less value. We thank Nicos Nicola for reviewing this manuscript and Peter Maltezos for figure production.

Declaration of interest: The authors were supported by the National Health and Medical Research Council (NHMRC), Australia (Program grant 461219, fellowship to SEN) and the National Institutes of Health, USA (Grant CA022556-33). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.