Suppressor of cytokine signalling (SOCS) 1 and 3 enhance cell adhesion and inhibit migration towards the chemokine eotaxin/CCL11

Stevenson, Nigel J.; McFarlane, Cheryl; Ong, Seow Theng; Nahlik, Krystyna; Kelvin, Alyson A.; Addley, Mark; Long, Aideen; Greaves, David R.; O’Farrelly, Cliona; Johnston, James A.

doi:10.1016/j.febslet.2010.10.007

Cited by 12 publications

(9 citation statements)

References 28 publications

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“…When the ratio of activity of these small GTPases is no longer optimal for the protrusion and polarization of the cell, migration will be influenced (40). Constitutively active RhoA may impede cell motility (20,41,42). One of the downstream effectors of RhoA is Rho kinase, which can be effectively inhibited by the compound Y-27632 (28,43).…”

Section: Discussionmentioning

confidence: 99%

Slit2 Regulates the Dispersal of Oligodendrocyte Precursor Cells via Fyn/RhoA Signaling

Liu¹,

Lü²,

Zhang

et al. 2012

Journal of Biological Chemistry

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Background: Secreted by nervous system midline cells Slits regulate neurodevelopmental processes through binding to roundabout receptors (Robos). Results: Slit2 causes dispersal of oligodendrocyte precursor cells (OPCs) by inducing the association between Robo1 and Fyn. Conclusion: Robo1 interacts with Fyn to repel the migration of OPCs through RhoA activation. Significance: Learning how Slit/Robo signaling regulates OPC dispersal is crucial for understanding the distribution of OPCs during central nervous system development.

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Section: Discussionmentioning

confidence: 99%

Slit2 Regulates the Dispersal of Oligodendrocyte Precursor Cells via Fyn/RhoA Signaling

Liu¹,

Lü²,

Zhang

et al. 2012

Journal of Biological Chemistry

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“…More recently, we have shown that SOCS3 also inhibits granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-4 signalling to regulate dendritic cell (DC) maturation [10] and that SOCS3 targets focal adhesion kinase (FAK) and Ras homolog gene family, member A (RhoA) to block migration towards the allergic chemokine CCL11 [11]. A key role for SOCS3 in the regulation of IL-6 signalling was identified by conditional knock out (KO) of SOCS3 in murine liver and macrophages, resulting in prolonged activation of STAT1 and STAT3 [8], while an inhibitory role for SOCS3 in IFN signalling has been widely documented to confer resistance to treatment for Hepatitic C virus (HCV) infection [12].…”

Section: Introductionmentioning

confidence: 99%

miR-19a: An Effective Regulator of SOCS3 and Enhancer of JAK-STAT Signalling

et al. 2013

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Suppressors of cytokine signalling (SOCS) proteins are classic inhibitors of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Many cytokines and pathogenic mediators induce expression of SOCS, which act in a negative feedback loop to inhibit further signal transduction. SOCS mRNA expression is regulated by DNA binding of STAT proteins, however, their post-transcriptional regulation is poorly understood. microRNAs (miRNAs) are small non-coding RNAs that bind to complementary sequences on target mRNAs, often silencing gene expression. miR-19a has been shown to regulate SOCS1 expression during mutiple myeloma and be induced by the anti-viral cytokine interferon-(IFN)-α, suggesting a role in the regulation of the JAK-STAT pathway. This study aimed to identify targets of miR-19a in the JAK-STAT pathway and elucidate the functional consequences. Bioinformatic analysis identified highly conserved 3’UTR miR-19a target sequences in several JAK-STAT associated genes, including SOCS1, SOCS3, SOCS5 and Cullin (Cul) 5. Functional studies revealed that miR-19a significantly decreased SOCS3 mRNA and protein, while a miR-19a antagomir specifically reversed its inhibitory effect. Furthermore, miR-19a-mediated reduction of SOCS3 enhanced IFN-α and interleukin (IL)-6 signal transduction through STAT3. These results reveal a novel mechanism by which miR-19a may augment JAK-STAT signal transduction via control of SOCS3 expression and are fundamental to the understanding of inflammatory regulation.

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“…As shown in Figure 2, SOCS1 localizes to the microtubule organizing center (MTOC) (44) as does SOCS3 (45). Both SOCS1 and SOCS3 enhance FAK- and RhoA-activation leading to increased cell adhesion and reduced migration (46). …”

Section: Host Cell Cytoskeletal Reorganization Mediated By Ifn-γmentioning

confidence: 99%

Complexity of Interferon-γ Interactions with HSV-1

Bigley

2014

Front. Immunol.

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The intricacies involving the role of interferon-gamma (IFN-γ) in herpesvirus infection and persistence are complex. Herpes simplex virus type 1 (HSV-1) uses a variety of receptors to enter cells and is transported to and from the host cell nucleus over the microtubule railroad via retrograde and anterograde transport. IFN-γ exerts dual but conflicting effects on microtubule organization. IFN-γ stimulates production of suppressors of cytokine signaling 1 and 3 (SOCS1 and SOCS3), which are involved in microtubule stability and are negative regulators of IFN-γ signaling when overexpressed. IFN-γ also interferes with the correct assembly of microtubules causing them to undergo severe bundling, contributing to its anti-viral effect. Factors leading to the decision for a replicative virus lytic cycle or latency in the trigeminal ganglion (TG) occur on histone 3 (H3), involve IFN-γ produced by natural killer cells and non-cytolytic CD8+T cells, SOCS1, SOCS3, and M2 anti-inflammatory microglia/macrophages maintained by inhibitory interleukin 10 (IL-10). Both M2 microglia and CD4+CD25+Foxp3+ Treg cells produce IL-10. Histone deacetylases (HDACs) are epigenetic regulators maintaining chromatin in an inactive state necessary for transcription of IFN-γ-activated genes and their anti-viral effect. Following inhibition of HDACs by stressors such as ultraviolet light, SOCS1 and SOCS3 are acetylated, and chromatin is relaxed and available for virus replication. SOCS1 prevents expression of MHC class 1 molecules on neuronal cells and SOCS3 attenuates cytokine-induced inflammation in the area. A model is presented to unify the effects of IFN-γ, SOCS1, SOCS3, and HSV-1 on H3 and chromatin structure in virus latency or reactivation. HSV-1 latency in the TG is viewed as an active ongoing process involving maintenance of microglia in an M2 anti-inflammatory state by IL-10. IL-10 is produced in an autocrine manner by the M2 microglia/macrophages and by virus-specific CD4+Foxp3+ Treg cells interacting with virus-specific non-cytolytic CD8+ T cells.

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Suppressor of cytokine signalling (SOCS) 1 and 3 enhance cell adhesion and inhibit migration towards the chemokine eotaxin/CCL11

Cited by 12 publications

References 28 publications

Slit2 Regulates the Dispersal of Oligodendrocyte Precursor Cells via Fyn/RhoA Signaling

Slit2 Regulates the Dispersal of Oligodendrocyte Precursor Cells via Fyn/RhoA Signaling

miR-19a: An Effective Regulator of SOCS3 and Enhancer of JAK-STAT Signalling

Complexity of Interferon-γ Interactions with HSV-1

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