Structure‐activity studies of peptidomimetics based on kinase‐inhibitory region of suppressors of cytokine signaling 1

2018 ◽  
Vol 110 (5) ◽  
pp. e23082 ◽  
Author(s):  
Sara La Manna ◽  
Laura Lopez‐Sanz ◽  
Marilisa Leone ◽  
Paola Brandi ◽  
Pasqualina Liana Scognamiglio ◽  
...  
Keyword(s):  
Cytokine Signaling ◽  
Structure Activity ◽  
Inhibitory Region ◽  
Suppressors Of Cytokine Signaling ◽  
Kinase Inhibitory Region

Cyclic mimetics of Kinase-Inhibitory Region of Suppressors of Cytokine Signaling 1: progress toward novel anti-inflammatory therapeutics

2021 ◽  
pp. 113547
Author(s):  
Sara La Manna ◽  
Laura Lopez-Sanz ◽  
Susana Bernal ◽  
Sara Fortuna ◽  
Flavia A. Mercurio ◽  
...  
Keyword(s):  
Cytokine Signaling ◽  
Inhibitory Region ◽  
Suppressors Of Cytokine Signaling ◽  
Anti Inflammatory ◽  
Kinase Inhibitory Region

scholarly journals Both the Suppressor of Cytokine Signaling 1 (SOCS-1) Kinase Inhibitory Region and SOCS-1 Mimetic Bind to JAK2 Autophosphorylation Site: Implications for the Development of a SOCS-1 Antagonist

2007 ◽  
Vol 178 (8) ◽  
pp. 5058-5068 ◽  
Author(s):  
Lilian W. Waiboci ◽  
Chulbul M. Ahmed ◽  
Mustafa G. Mujtaba ◽  
Lawrence O. Flowers ◽  
James P. Martin ◽  
...  
Keyword(s):  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Inhibitory Region ◽  
Autophosphorylation Site ◽  
Kinase Inhibitory Region

scholarly journals AI-11 The kinase inhibitory region of suppressor of cytokine signaling-1 modulates autoinflammatory skin pathology

2018 ◽  
Author(s):  
Antia E Veal ◽  
Brandon Lam ◽  
Teresa Collins ◽  
Joseph Larkin
Keyword(s):  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Inhibitory Region ◽  
Kinase Inhibitory Region

scholarly journals Estrogen Up-Regulates Hepatic Expression of Suppressors of Cytokine Signaling-2 and -3 in Vivo and in Vitro

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5525-5531 ◽  
Author(s):  
Gary M. Leong ◽  
Sofia Moverare ◽  
Jesena Brce ◽  
Nathan Doyle ◽  
Klara Sjögren ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Hepatoma Cells ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Wild Type ◽  
Hepatic Expression ◽  
Suppressors Of Cytokine Signaling

Abstract Suppressors of cytokine signaling (SOCS) are important negative regulators of cytokine action. We recently reported that estrogen stimulates SOCS-2 expression and inhibits GH signaling in kidney cells. The effects of estrogen on SOCS expression in other tissues are unclear. The aim of this study was to investigate in vivo and in vitro whether estrogen affected SOCS expression in the liver, a major target organ of GH. The in vivo hepatic effects of estrogen on ovariectomized mice lacking estrogen receptor (ER)-α, ERβ, or both and their wild-type littermates were examined by DNA microarray analysis. In vitro, the effects of estrogen on SOCS expression in human hepatoma cells were examined by reverse transcription quantitative PCR. Long-term (3 wk) estrogen treatment induced a 2- to 3-fold increase in hepatic expression of SOCS-2 and -3 in wild-type and ERβ knockout mice but not in those lacking ERα or both ER subtypes. Short-term treatment (at 24 h) increased the mRNA level of SOCS-3 but not SOCS-2. In cultured hepatoma cells, estrogen increased SOCS-2 and -3 mRNA levels by 2-fold in a time- and dose-dependent manner (P < 0.05). Estrogen induced murine SOCS-3 promoter activity by 2-fold (P < 0.05) in constructs containing a region between nucleotides −1862 and −855. Moreover, estrogen and GH had additive effects on the SOCS-3 promoter activity. In summary, estrogen, via ERα, up-regulated hepatic expression of SOCS-2 and -3, probably through transcriptional activation. This indicates a novel mechanism of estrogen regulation of cytokine action.

New mimetic peptides of the kinase-inhibitory region (KIR) of SOCS1 through focused peptide libraries

2012 ◽  
Vol 443 (1) ◽  
pp. 231-240 ◽  
Author(s):  
Nunzianna Doti ◽  
Pasqualina L. Scognamiglio ◽  
Stefania Madonna ◽  
Claudia Scarponi ◽  
Menotti Ruvo ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Catalytic Site ◽  
Janus Kinase ◽  
Scanning Method ◽  
Expression Levels ◽  
Interferon Regulatory Factor 1 ◽  
Inhibitory Region ◽  
Inflammatory Processes ◽  
Cytokine Stimulation ◽  
Kinase Inhibitory Region

SOCS (suppressor of cytokine signalling) proteins are negative-feedback regulators of the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) pathway. Their expression levels are low under physiological conditions, but they are up-regulated in response to cytokine stimulation in many immune and inflammatory processes. Overexpression of SOCS1 in keratinocyte clones abrogates the IFNγ (interferon γ)-induced expression of many pro-inflammatory genes and the release of related chemokines by blocking the JAK/STAT pathway. SOCS1 inhibits JAK2 kinase activity by binding the catalytic site of JAK2, with its KIR (kinase-inhibitory region) acting as a pseudo-substrate of the enzyme. In the present study, we screened a focused combinatorial peptide library of KIR to identify new peptides able to mimic its function with an improved affinity towards the JAK2 catalytic site. Using an alanine-scanning method, KIR residues that are crucial for the interaction with JAK2 were unveiled. In this way, the KIR sequence was restricted to a shorter segment and ‘non-essential’ residues were replaced by different amino acids following a simplified combinatorial approach. We selected a new unnatural sequence able to bind to JAK2 with Kd values in the nanomolar range. This peptide was tested in human keratinocyte cultures and reduced the phosphorylation of STAT1 and the expression levels of IRF-1 (interferon regulatory factor-1).

Misregulation of suppressors of cytokine signaling in eosinophilic esophagitis

2012 ◽  
Vol 48 (8) ◽  
pp. 910-920 ◽  
Author(s):  
Mª Paz Zafra ◽  
Natally Cancelliere ◽  
Pablo Rodríguez del Río ◽  
Mónica Ruiz-García ◽  
Laura Estévez ◽  
...  
Keyword(s):  
Eosinophilic Esophagitis ◽  
Cytokine Signaling ◽  
Suppressors Of Cytokine Signaling

scholarly journals Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and function

2009 ◽  
Vol 30 (12) ◽  
pp. 592-602 ◽  
Author(s):  
Douglas C. Palmer ◽  
Nicholas P. Restifo
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
T Cell Differentiation ◽  
Cytokine Signaling ◽  
Suppressors Of Cytokine Signaling ◽  
And Function

Overexpression of suppressors of cytokine signaling 1 regulate the proliferation and differentiation of rat-derived neural stem cells

2017 ◽  
Vol 119 (7) ◽  
pp. 680-688 ◽  
Author(s):  
Meng Cui ◽  
Xin-Long Ma ◽  
Jie Sun ◽  
Jin-Quan He ◽  
Lin Shen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cytokine Signaling ◽  
Proliferation And Differentiation ◽  
Suppressors Of Cytokine Signaling
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