ArticleThe Journal of biological chemistry2016
Suppressor of Cytokine Signaling (SOCS)1 Regulates Interleukin-4 (IL-4)-activated Insulin Receptor Substrate (IRS)-2 Tyrosine Phosphorylation in Monocytes and Macrophages via the Proteasome.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
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- Alveolar macrophage-neutrophil crosstalk in acute lung injury: mechanisms, feedback loops, and therapeutic opportunities.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Ubiquitination regulates allergic asthma by affecting immune cells and immune responses.Biochemistry and biophysics reports · 2025Review
- The Role of Ubiquitin-Proteasome System (UPS) in Asthma Pathology.Journal of asthma and allergy · 2025Review
- CD23Science translational medicine · 2024Article
- Systematic identification of genotype-dependent enhancer variants in eosinophilic esophagitis.American journal of human genetics · 2024Article
- SOCS1 is a critical checkpoint in immune homeostasis, inflammation and tumor immunity.Frontiers in immunology · 2024Review
- The Role of Insulin Receptor Substrate Proteins in Bronchopulmonary Dysplasia and Asthma: New Potential Perspectives.International journal of molecular sciences · 2022Review
- Modulation of IL-4/IL-13 cytokine signaling in the context of allergic disease.The Journal of allergy and clinical immunology · 2022Review
- AMPK suppresses Th2 cell responses by repressing mTORC2.Experimental & molecular medicine · 2022Article
- Ginkgo Biloba Leaf Extract Improves an Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer's Disease Patients.Nutrients · 2022Article
- Open label safety and efficacy pilot to study mitigation of equine recurrent uveitis through topical suppressor of cytokine signaling-1 mimetic peptide.Scientific reports · 2022Article
- Hyperuricemia contributes to glucose intolerance of hepatic inflammatory macrophages and impairs the insulin signaling pathwayFrontiers in immunology · 2022Article
- What does elevated TARC/CCL17 expression tell us about eosinophilic disorders?Seminars in immunopathology · 2021Review
- Mitochondrial Mutations and Genetic Factors Determining NAFLD Risk.International journal of molecular sciences · 2021Review
- Suppressor of cytokine signaling-1 mimetic peptides attenuate lymphocyte activation in the MRL/lpr mouse autoimmune model.Scientific reports · 2021Article
- M-CSF, IL-6, and TGF-β promote generation of a new subset of tissue repair macrophage for traumatic brain injury recovery.Science advances · 2021Article
- A data-driven computational model enables integrative and mechanistic characterization of dynamic macrophage polarization.iScience · 2021Article
- Sex differences in M2 polarization, chemokine and IL-4 receptors in monocytes and macrophages from asthmatics.Cellular immunology · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Allergic asthma is a chronic lung disease initiated and driven by Th2 cytokines IL-4/-13. In macrophages, IL-4/-13 bind IL-4 receptors, which signal through insulin receptor substrate (IRS)-2, inducing M2 macrophage differentiation. M2 macrophages correlate with disease severity and poor lung function, although the mechanisms that regulate M2 polarization are not understood. Following IL-4 exposure, suppressor of cytokine signaling (SOCS)1 is highly induced in human monocytes. We found that siRNA knockdown of SOCS1 prolonged IRS-2 tyrosine phosphorylation and enhanced M2 differentiation, although siRNA knockdown of SOCS3 did not affect either. By co-immunoprecipitation, we found that SOCS1 complexes with IRS-2 at baseline, and this association increased after IL-4 stimulation. Because SOCS1 is an E3 ubiquitin ligase, we examined the effect of proteasome inhibitors on IL-4-induced IRS-2 phosphorylation. Proteasomal inhibition prolonged IRS-2 tyrosine phosphorylation, increased ubiquitination of IRS-2, and enhanced M2 gene expression. siRNA knockdown of SOCS1 inhibited ubiquitin accumulation on IRS-2, although siRNA knockdown of SOCS3 had no effect on ubiquitination of IRS-2. Monocytes from healthy and allergic individuals revealed that SOCS1 is induced by IL-4 in healthy monocytes but not allergic cells, whereas SOCS3 is highly induced in allergic monocytes. Healthy monocytes displayed greater ubiquitination of IRS-2 and lower M2 polarization than allergic monocytes in response to IL-4 stimulation. Here, we identify SOCS1 as a key negative regulator of IL-4-induced IRS-2 signaling and M2 differentiation. Our findings provide novel insight into how dysregulated expression of SOCS increases IL-4 responses in allergic monocytes, and this may represent a new therapeutic avenue for managing allergic disease.
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