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Cited by 470Cytokine Signaling Pathways and InteractionsReceptor Mechanisms and SignalingProtein Tyrosine Phosphatases

Biology and significance of the JAK/STAT signalling pathways

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Kiu, Hiu, Nicholson, Sandra E.·2012·Growth Factors
DOI 10.3109/08977194.2012.660936PMC PMC3762697
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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.

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  • Many cytokines bind receptors composed of heterologous polypeptide chains, several of which are shared; a single or combination of two to three JAKs selectively associates with each receptor, and a combination of different STATs can be activated by a single cytokine.

    “Many cytokines bind to receptors composed of heterologous polypeptide chains, and several of the polypeptide chains are common or shared. In addition, a single or combination of two to three JAKs selectively associates with each receptor (Lin et al., 1995; Baker et al., 2007; Kiu and Nicholson, 2012) (Fig. 2). The consequence is that a combination of different STATs can be activated by a single cy”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Kiu and Nicholson, 2012

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Authors
Kiu, H., & Nicholson, S. E.
Affiliations
  • Walter and Eliza Hall Institute of Medical Research (AU)
  • The University of Melbourne (AU)
Corresponding author
Nicholson, Sandra E.
ORCID
Nicholson, Sandra E.
Venue
Growth Factors
Publisher
Informa UK Limited
Published
2012-02-20
Volume
30
Issue
2
Pages
88-106
ISSN
  • 0897-7194 (ISSN-L)
  • 1029-2292
DOI
10.3109/08977194.2012.660936
PMC
PMC3762697
OpenAlex
W2075490622
Cited by
470
References
17
Citations by year
2026: 20 · 2025: 25 · 2024: 38 · 2023: 44 · 2022: 39 · 2021: 52 · 2020: 44 · 2019: 40 · 2018: 28 · 2017: 31 · 2016: 25 · 2015: 23 · 2014: 34 · 2013: 23 · 2012: 3
FWCI
2.75
Type
journal article
Language
en
Open access
Locations
  • Growth Factors (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R37CA022556, CA022556-33, R01CA022556)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
JAK/STAT signaling, Janus kinase, signal transducer and activator of transcription, cytokine signaling, growth factor signaling, transcriptional regulation, JAK inhibitors, pathogenesis
MeSH terms
Animals, Clinical Trials as Topic, Gene Expression Regulation, Humans, Mutation, Myeloproliferative Disorders, Nitriles, Pyrazoles, Pyrimidines, Signal Transduction, Treatment Outcome, STAT Transcription Factors, Mice, Janus Kinases

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