Ask about this productRelated genes to: SOCS3 antibody
- Gene:
- SOCS3 NIH gene
- Name:
- suppressor of cytokine signaling 3
- Previous symbol:
- -
- Synonyms:
- SSI-3, CIS3, SOCS-3, Cish3
- Chromosome:
- 17q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-11-13
- Date modifiied:
- 2019-04-23
Related products to: SOCS3 antibody
Related articles to: SOCS3 antibody
- Glucagon is a key hormone regulating gluconeogenesis and glucose homeostasis in mammals, yet its regulatory mechanisms in glucose metabolism in carnivorous fish remain incompletely understood. To systematically investigate glucagon-mediated glucose metabolism in Japanese flounder (), liver samples were collected before glucagon injection (0 h) and at 1 h and 6 h post-injection for transcriptome sequencing (RNA-seq). Transcriptome analysis identified numerous differentially expressed genes involved in glucose and energy metabolism. In total, 507, 1458, and 709 differentially expressed genes were detected in the comparisons of 0 h vs 1 h, 1 h vs 6 h, and 0 h vs 6 h, respectively. KEGG enrichment analysis showed that glucagon activated pathways related to glucagon signaling, insulin resistance, FoxO signaling, and energy metabolism, including AMPK and PPAR pathways, suggesting that glucagon rapidly stimulates gluconeogenesis. At 6 h post-injection, genes involved in glycolysis and glucose transport were upregulated, whereas key gluconeogenic genes were downregulated, indicating attenuation of glucagon-induced metabolic responses. Further analysis showed that glucagon suppressed the insulin-mediated PI3K/AKT signaling pathway. Among the candidate genes, SOCS3 and TRIB3 were upregulated and may serve as key regulators linking glucagon and insulin signaling. Functional experiments further showed that knockdown of TRIB3 reduced glucose levels in hepatocyte culture medium and increased the expression of insulin signaling-related genes. Overall, glucagon regulates glucose metabolism in Japanese flounder by promoting gluconeogenesis while suppressing insulin signaling, providing transcriptomic insights into endocrine regulation in carnivorous fish. - Source: PubMed
Publication date: 2026/04/16
Zhang TingWang HongquanXiao TiaoyiYang MengxiZhang Wenbing - Suppressor of Cytokine Signaling 3 (SOCS3) is a pivotal negative regulator of the JAK/STAT pathway, and its loss or silencing is frequently associated with hyperactivated STAT3 signaling in aggressive cancers, including Triple-Negative Breast Cancer (TNBC). In this study, we present the rational design, biophysical characterization, and cellular evaluation of novel SOCS3-derived peptidomimetics that incorporate a hitherto unexploited structural determinant of the SOCS3/JAK2/Gp130 interface: the BC loop. The synthesis of individual and chimeric peptides was guided by structural analysis of the ternary complex, which combined the KIR/ESS regions with a stabilized BC loop. The results of the study revealed that the chimeric construct, KIRESS BC loop-chim, exhibited markedly improved affinity for JAK2 ( ∼ 10 μM) in comparison to the affinity of the isolated regions. This was determined by means of MicroScale Thermophoresis (MST). Circular dichroism (CD) and fluorescence spectroscopy demonstrated that turn-inducing motifs stabilize native-like conformations, correlating with enhanced serum stability. To preliminarily evaluate potential cellular effects, we assessed their serum stabilities and their cytotoxicity in MDA-MB-231 and MDA-MB-468 cells once conjugated to a small Cell-Penetreting Peptide (CPP). In both cases, the good biocompatibility of the designed mimetics appeared promising for evaluating signaling-dependent effects. These findings validate a multiregion, structure-guided design strategy and identify an improved SOCS3 proteomimetic scaffold with potential for targeting dysregulated JAK/STAT signaling in cancer. - Source: PubMed
Publication date: 2026/04/13
Cugudda AlessiaLa Manna SaraBucciero CandidaCastellano GiulianoMalfitano Anna MariaMarasco Daniela - Interleukin-10 (IL-10) is a key immunoregulatory cytokine that suppresses inflammatory gene transcription in myeloid cells through signal transducer and activator of transcription 3 (STAT3). In Alzheimer's disease and neuroinflammation, microglia express and exhibit STAT3 Tyr705 phosphorylation following IL-10 stimulation, indicating IL-10 receptor-dependent STAT3 activation. Recent studies demonstrate that IL-10 induces promoter-selective STAT3-dependent transcriptional regulation in microglia through chromatin-associated mechanisms, whereas gp130-dependent cytokines activate STAT3 to induce transcription of defined target genes, including and . Following IL-10 receptor activation, STAT3 binds regulatory regions of inflammatory genes, including , and , with reduced RNA polymerase II and NF-κB binding. IL-10-dependent transcriptional repression involves formation of a nuclear SHIP1-STAT3 complex, localization of histone deacetylase (HDAC)1 and HDAC2 to H3K4me1-enriched enhancer regions, reduced H3K27ac, and decreased chromatin accessibility at regulatory regions of inflammatory genes. IL-10-activated STAT3 induces , which regulates JAK1 and TYK2 activity and STAT3 phosphorylation. Impairment of IL-10 receptor signaling in microglia is associated with increased inflammatory gene expression, enhanced inflammasome-related transcription, demyelination, and amyloid accumulation. This review focuses on IL-10-STAT3-dependent transcriptional regulation in microglia, including receptor signaling, chromatin-associated mechanisms, and disease-associated gene expression in Alzheimer's disease and neuroinflammation. - Source: PubMed
Publication date: 2026/04/05
Kim Mi EunLee Jun Sik - To regulate immune and inflammatory responses, suppressor of cytokine signalling (SOCS) proteins bind to multiple signalling components downstream of cytokine receptors, such as Janus kinase (JAK) and signal transducers and activators of transcription (STAT). Dysfunctional SOCS proteins in immune and tissue-resident cells may contribute to chronic inflammation. Abnormal expression of SOCS proteins, including SOCS1, SOCS2, SOCS3, SOCS5, SOCS6, and SOCS7, has been reported in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), playing a vital role in disease pathogenesis. The expression of SOCS1 and SOCS3 varies across different cell types and stages of the disease. Genetic polymorphisms, epigenetic modifications, microRNAs, cytokines, hormones, therapeutic agents, and gender factors can influence SOCS1 and SOCS3 expression in MS patients and EAE mice. The functional impact of SOCS1 and SOCS3 is cell-type specific, with distinct roles in T cell subsets, microglia/macrophages, dendritic cells, astrocytes, and oligodendrocytes. In particular, SOCS1 and SOCS3 affect T cell subset differentiation, Th17/Treg cell balance, microglial/macrophage polarization, dendritic cell functions, as well as oligodendrocyte survival and activity. Therapeutic approaches targeting SOCS molecules, including SOCS1 mimetic peptides, have demonstrated promise in EAE models. This review provides a comprehensive explanation regarding the expression patterns of SOCS molecules in MS patients and EAE model, factors affecting their expression and their mechanistic role in disease immunopathogenesis, as well as highlights their potential as a therapeutic target for MS. - Source: PubMed
Jafarzadeh AbdollahMikaeili NargesJafarzadeh Zahra - Aberrant activation of the Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathway is associated with various pathological conditions. Suppressor of Cytokine Signaling (SOCS) proteins are able to inhibit this pathway by competitively binding to the STAT binding sites on JAK kinases (blocking the binding of STATs to JAK kinases). However, the mechanism of selective inhibition of JAK kinases by SOCSs remains poorly understood. Here, we performed microsecond-scale molecular dynamics (MD) simulations combined with molecular mechanics/generalized born surface area (MM/GBSA) binding free energy calculations, covariance analysis, and principal component analysis (PCA) to systematically compare the binding characteristics of six distinct JAK/SOCS complexes. The MM/GBSA results showed that the binding affinity of SOCS1/SOCS3 to JAK1/TYK2 is significantly stronger than that of SOCS2 to JAK1/TYK2. Correspondingly, PCA and covariance analysis revealed that SOCS2 and JAK1/TYK2 moved toward the opposite directions during the simulation. All these indicate that SOCS1/SOCS3 binds more stably to JAK1/TYK2 than SOCS2, implying that SOCS1/SOCS3 has a better inhibitory effect on JAK1/TYK2. Furthermore, the results of energy decomposition residues and hydrogen bond analysis illustrated that the strong binding ability of SOCS1/SOCS3 to JAK1/TYK2 is based on the presence of "Y", "QR", and "FF" motifs (missing in the SOCS2) in its KIR region and BC loop, which are able to form stable hydrogen bond networks and Met-aromatic interactions with the GQM motifs of JAK1/TYK2. This might be the fundamental reason why SOCS1/SOCS3 has a significantly stronger selective inhibitory effect on JAK1/TYK2 than SOCS2. Our work elucidates the dynamic structural basis of JAK/SOCS binding selectivity at the atomic level, providing new insights into the mechanism of JAK kinase selectivity and laying the foundation for the development of structure-based JAK1/TYK2-targeted cancer therapy drugs. - Source: PubMed
Publication date: 2026/04/27
Zhai XinmiaoLi YanYang Yong-BiaoLiu YeChu Huiying