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Cited by 1,149Cytokine Signaling Pathways and InteractionsImmunodeficiency and Autoimmune DisordersProtein Tyrosine Phosphatases

Janus kinases in immune cell signaling

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Ghoreschi, Kamran, Laurence, Arian, O’Shea, John J.·2009·Immunological Reviews
DOI 10.1111/j.1600-065x.2008.00754.xPMC PMC2782696
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Abstract

Summary: The Janus family kinases (Jaks), Jak1, Jak2, Jak3, and Tyk2, form one subgroup of the non‐receptor protein tyrosine kinases. They are involved in cell growth, survival, development, and differentiation of a variety of cells but are critically important for immune cells and hematopoietic cells. Data from experimental mice and clinical observations have unraveled multiple signaling events mediated by Jaks in innate and adaptive immunity. Deficiency of Jak3 or Tyk2 results in defined clinical disorders, which are also evident in mouse models. A striking phenotype associated with inactivating Jak3 mutations is severe combined immunodeficiency syndrome, whereas mutation of Tyk2 results in another primary immunodeficiency termed autosomal recessive hyperimmunoglobulin E syndrome. By contrast, complete deletion of Jak1 or Jak2 in the mouse are not compatible with life and, unsurprisingly, do not have counterparts in human disease. However, activating mutations of each of the Jaks are found in association with malignant transformation, the most common being gain‐of‐function mutations of Jak2 in polycythemia vera and other myeloproliferative disorders. Our existing knowledge on Jak signaling pathways and fundamental work on their biochemical structure and intracellular interactions allow us to develop new strategies for controlling autoimmune diseases or malignancies by developing selective Jak inhibitors, which are now coming into clinical use. Despite the fact that Jaks were discovered only a little more than a decade ago, at the time of writing there are 20 clinical trials underway testing the safety and efficacy of Jak inhibitors.

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  • JAK1 and JAK2 deficiency is embryonically lethal due to neurologic defects and deficiencies in erythropoiesis, respectively; JAK3 and TYK2 deficiencies are associated with severe immunodeficiency syndromes in animal models and humans.

    “Their essential role in developmental biology is underscored by the fact that deficiency in JAK1 and JAK2 is embryonically lethal due to neurologic defects and deficiencies in erythropoiesis, respectively, whereas deficiencies in JAK3 and TYK2 are associated with a variety of severe immunodeficiency syndromes in animal models and humans (Ghoreschi et al., 2009).”

    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 Ghoreschi et al., 2009

    The Jak1 deficiency section describes Jak1-knockout mice as perinatally lethal, probably due to neurological deficits—not embryonically lethal. The Jak2 deficiency section reports embryonic lethality from defective erythropoiesis, while the sections on Jak3 and Tyk2 describe immunodeficiency in humans and mouse models. (LLM, conf=0.90)

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Authors
Ghoreschi, K., Laurence, A., & O’Shea, J. J.
Affiliations
National Institutes of Health (US)
Corresponding author
Ghoreschi, Kamran
ORCID
Venue
Immunological Reviews
Publisher
Wiley
Published
2009-03
Volume
228
Issue
1
Pages
273-287
ISSN
  • 0105-2896 (ISSN-L)
  • 1600-065X
DOI
10.1111/j.1600-065x.2008.00754.x
PMC
PMC2782696
OpenAlex
W2151734278
Cited by
1,149
References
1
Citations by year
2026: 34 · 2025: 64 · 2024: 76 · 2023: 100 · 2022: 74 · 2021: 85 · 2020: 102 · 2019: 77 · 2018: 52 · 2017: 58 · 2016: 72 · 2015: 63 · 2014: 60 · 2013: 75 · 2012: 60
FWCI
4.62
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5 d)
Locations
  • Immunological Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (Z01AR041106)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
Janus kinase, JAK1, JAK2, JAK3, TYK2, non-receptor tyrosine kinase, immune cell signaling, innate immunity, adaptive immunity, severe combined immunodeficiency, polycythemia vera, myeloproliferative neoplasms, JAK inhibitors, autoimmune disease, hematopoietic cells
MeSH terms
Animals, Humans, Myeloproliferative Disorders, Signal Transduction, Severe Combined Immunodeficiency, Janus Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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