Cytokine Signalling Forum


Cytokine receptor signaling through the Jak–Stat–Socs pathway in disease

O'Sullivan LA, Liongue C, Lewis RS, et al. - Molecular Immunology 2007; 44:2497-506

This review from 2007 provides an overview of the largest cytokine receptor family, the haematopoietin receptors, as well as other key components involved in one of the major cytokine signalling pathways implicated in autoimmune and inflammatory diseases. This includes the Janus kinases (Jaks), signal transducers and activators of transcription (Stats) and suppressors of cytokine signalling genes (Socs). Essentially, when a cytokine binds to a receptor from this group a functional cytokine receptor complex is formed, provided a cytoplasmic kinase such as Jak is able to initiate the intracellular signalling reaction. The Jak protein then phosphorylates a tyrosine residue within the receptor and dormant cytoplasmic proteins such as Stats are then able to bind. Once bound, Stats undergo a conformational change which allows them to act as a transcription factor and regulate gene expression of target genes including Socsgenes. This process generally acts as a feedback loop to suppress further signalling. This pathway is reviewed in detail and the role of each component discussed. [Note: At the time this article was written, tofacitinib was under investigation in phase 2 trials for rheumatoid arthritis, psoriasis, and the prevention of renal transplant rejection]

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Upload date: June 2013

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