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Updated: Feb 4, 2026
Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells
Published on: September 9, 2021
The molecular details of cytokine signaling via the JAK/STAT pathway
Rhiannon Morris1,2, Nadia J Kershaw1,2, Jeffrey J Babon1,2
1Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3052, Victoria, Australia.
Abstract:
More than 50 cytokines signal via the JAK/STAT pathway to orchestrate hematopoiesis, induce inflammation and control the immune response. Cytokines are secreted glycoproteins that act as intercellular messengers, inducing proliferation, differentiation, growth, or apoptosis of their target cells. They act by binding to specific receptors on the surface of target cells and switching on a phosphotyrosine-based intracellular signaling cascade initiated by kinases then propagated and effected by SH2 domain-containing transcription factors. As cytokine signaling is proliferative and often inflammatory, it is tightly regulated in terms of both amplitude and duration. Here we review molecular details of the cytokine-induced signaling cascade and describe the architectures of the proteins involved, including the receptors, kinases, and transcription factors that initiate and propagate signaling and the regulatory proteins that control it.
Insights
Cytokines use the JAK/STAT pathway to regulate cell functions. This review details the molecular mechanisms and protein structures involved in this critical signaling pathway.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Cytokines are key intercellular messengers regulating vital cellular processes.
- The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is crucial for immune responses and hematopoiesis.
- Dysregulated cytokine signaling can lead to inflammatory conditions.
Purpose of the Study:
- To provide a comprehensive review of the molecular details of cytokine-induced signaling.
- To describe the protein architectures involved in the JAK/STAT pathway.
- To highlight the regulatory mechanisms controlling cytokine signaling amplitude and duration.
Main Methods:
- Review of existing literature on cytokine signaling and the JAK/STAT pathway.
- Analysis of molecular mechanisms of receptor binding and signal transduction.
- Examination of the structural characteristics of key proteins: receptors, kinases, and transcription factors.
Main Results:
- Detailed elucidation of the phosphotyrosine-based intracellular signaling cascade initiated by kinases.
- Description of the roles of SH2 domain-containing transcription factors in signal propagation.
- Identification of critical regulatory proteins that control signal amplitude and duration.
Conclusions:
- The JAK/STAT pathway is a complex signaling network essential for cellular communication.
- Understanding the molecular intricacies and protein structures is vital for comprehending immune and hematopoietic regulation.
- Tight regulation of this pathway is necessary to prevent excessive proliferation and inflammation.
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