Cited by 258Cytokine Signaling Pathways and InteractionsProtein Tyrosine PhosphatasesNF-κB Signaling Pathways

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Negative regulation of cytokine signaling

Greenhalgh, Christopher J, Hilton, Douglas J·2001·Journal of Leukocyte Biology

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Abstract

Cytokines use complex signaling cascades to elicit their biological effects, many of which involve phosphorylation as a mechanism of activation. Rapid and efficient attenuation of cytokine signals is crucial to maintaining regulation of these processes and to preventing toxic side effects. Phosphatases have been shown to be involved in these regulatory processes, but more recent research has seen the discovery of two new families of negative regulators, the suppressor of cytokine signaling (SOCS) and protein inhibitors of signal transducer and activator of transcription (STAT) (PIAS) protein families. SOCS proteins are induced by and inhibit many cytokine-signaling systems in a classic negative-feedback loop, and the generation of transgenic and knockout models has greatly increased our understanding of their physiological functions. PIAS proteins interact with the transcriptional mediators of cytokine action, the STATs, to suppress their DNA-binding activity. These three classes of molecules form what is now emerging as an integrated system for deactivating cytokine signaling at a number of levels, from the receptor to the transcription factor.

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Authors: Greenhalgh, C. J., & Hilton, D. J.
Affiliations: Walter and Eliza Hall Institute of Medical Research (AU)
Corresponding author: Greenhalgh, Christopher J
ORCID: Hilton, Douglas J
Venue: Journal of Leukocyte Biology
Publisher: Oxford University Press (OUP)
Published: 2001-09-01
Volume: 70
Issue: 3
Pages: 348-356
ISSN: 0741-5400 (ISSN-L)
1938-3673
DOI: 10.1189/jlb.70.3.348
OpenAlex: W2107469094
Cited by: 258
References: 93
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 11 · 2016: 14 · 2015: 9 · 2014: 13 · 2013: 11 · 2012: 13
FWCI: 10.00
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: Journal of Leukocyte Biology (publishedVersion)
PubMed (publishedVersion)
Funders: Anti-Cancer Council of Victoria, Melbourne, Australia
National Health and Medical Research Council, Canberra, Australia
National Institutes of Health (CA-22556)
Australian Federal Government Cooperative Research Centers Program
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: cytokine signaling, negative regulation, suppressor of cytokine signaling, STAT proteins, negative feedback loop, signal attenuation, protein phosphatase, transcriptional repression, DNA-binding activity
MeSH terms: Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling 3 Protein, Animals, Carrier Proteins, DNA-Binding Proteins, Models, Biological, Proteins, Repressor Proteins, Transcription Factors, Signal Transduction, Trans-Activators, Cytokines, Protein Tyrosine Phosphatases, Intracellular Signaling Peptides and Proteins, Suppressor of Cytokine Signaling Proteins, Protein Inhibitors of Activated STAT, Mice

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