The JAK/STAT signaling pathway
Abstract
The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeostasis in animals, from humans to flies. In mammals, the JAK/STAT pathway is the principal signaling mechanism for a wide array of cytokines and growth factors. JAK activation stimulates cell proliferation, differentiation, cell migration and apoptosis. These cellular events are critical to hematopoiesis, immune development, mammary gland development and lactation, adipogenesis, sexually dimorphic growth and other processes. Predictably, mutations that reduce JAK/STAT pathway activity affect these processes (reviewed by Igaz et al., 2001; O'Shea et al., 2002). Conversely, mutations that constitutively activate or fail to regulate JAK signaling properly cause inflammatory disease, erythrocytosis, gigantism and an array of leukemias. Here we present a general overview of the JAK/STAT pathway and illustrate the primary mechanisms of activation and regulation of this essential signaling cascade.Mechanistically, JAK/STAT signaling is relatively simple, with only a few principal components (for reviews, see Aaronson and Horvath, 2002; Heinrich et al., 2003; Kisseleva et al., 2002; O'Shea et al., 2002). As described above, a variety of ligands and their receptors stimulate the JAK/STAT pathway. Intracellular activation occurs when ligand binding induces the multimerization of receptor subu…
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The JAK/STAT pathway is activated by many protein ligands, including cytokines, growth factors, interferons, and peptide hormones, and regulates cell growth, proliferation, differentiation, and apoptosis.
“This pathway is activated in response to many protein ligands, including cytokines, growth factors, interferons (IFNs), and peptide hormones, where it regulates a wide range of cellular processes, including cell growth, proliferation, differentiation, and apoptosis (Rawlings et al., 2004; O’Shea et al., 2013).”
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 Rawlings et al., 2004
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“Mechanistically, JAK/STAT signaling is relatively simple, with only a few principal components (for reviews, see Aaronson and Horvath, 2002; Heinrich et al., 2003; Kisseleva et al., 2002; O’Shea et al., 2002).”
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- Authors
- Rawlings, J. S., Rosler, K. M., & Harrison, D. A.
- Affiliations
- University of Kentucky (US)
- University of Kentucky, Department of Biology, 101 T.H. Morgan Bldg., Lexington, KY 40506, USA
- Corresponding author
- Harrison, Douglas A.
- ORCID
- Harrison, Douglas A.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2004-03-15
- Volume
- 117
- Issue
- 8
- Pages
- 1281-1283
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2159659449
- Cited by
- 1,858
- References
- 2
- Citations by year
- 2026: 37 · 2025: 73 · 2024: 93 · 2023: 135 · 2022: 122 · 2021: 186 · 2020: 173 · 2019: 144 · 2018: 124 · 2017: 98 · 2016: 97 · 2015: 88 · 2014: 99 · 2013: 86 · 2012: 75
- FWCI
- 10.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- 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 › Cancer Research › NF-κB Signaling Pathways
- Keywords
- JAK/STAT signaling, Janus kinase, signal transducer and activator of transcription, cytokine signaling, receptor multimerization, transphosphorylation, transcriptional regulation, hematopoiesis, mammary gland development, adipogenesis, leukemia, inflammatory diseases, erythrocytosis, gigantism
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Models, Biological, Transcription, Genetic, Signal Transduction, Trans-Activators, Evolution, Molecular
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