scholarly journals Therapeutical potential of a peptide mimicking the SOCS1 kinase inhibitory region in skin immune responses

2013 ◽  
Vol 43 (7) ◽  
pp. 1883-1895 ◽  
Author(s):  
Stefania Madonna ◽  
Claudia Scarponi ◽  
Nunzianna Doti ◽  
Teresa Carbone ◽  
Andrea Cavani ◽  
...  
Keyword(s):  
Immune Responses ◽  
Inhibitory Region ◽  
Kinase Inhibitory Region

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).

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

Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain

1999 ◽  
Vol 4 (6) ◽  
pp. 339-351 ◽  
Author(s):  
Atsuo Sasaki ◽  
Hideo Yasukawa ◽  
Asuka Suzuki ◽  
Shintaro Kamizono ◽  
Takanori Syoda ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Sh2 Domain ◽  
Inhibitory Region ◽  
Kinase Inhibitory Region

scholarly journals A Cell Penetrating Peptide from SOCS-1 Prevents Ocular Damage in Experimental Autoimmune Uveitis

2018 ◽  
Author(s):  
Chulbul M. Ahmed ◽  
Michael T. Massengill ◽  
Cristhian J. Ildefonso ◽  
Howard M. Johnson ◽  
Alfred S. Lewin
Keyword(s):  
Adaptor Protein ◽  
Barrier Properties ◽  
Topical Administration ◽  
List Type ◽  
Potential Candidate ◽  
Experimental Autoimmune Uveitis ◽  
Autoimmune Uveitis ◽  
Inhibitory Region ◽  
Kinase Inhibitory Region ◽  
Experimental Autoimmune

AbstractWe describe an immunosuppressive peptide corresponding to the kinase inhibitory region (KIR) of the intracellular checkpoint protein suppressor of cytokine signaling 1 (SOCS-1) that binds to the phospho-tyrosine containing regions of the tyrosine kinases JAK2 and TYK2 and the adaptor protein MAL, and thereby inhibits signaling downstream from these signaling mediators. The peptide, SOCS1-KIR, is thus capable of downregulating overactive JAK/STAT or NF-kB signaling in somatic cells, including those in many compartments of the eye. Attachment of poly-arginine to this peptide (R9-SOCS1-KIR) allows it to penetrate the plasma membrane in aqueous media. R9-SOCS1-KIR was tested in ARPE-19 cells and was found to attenuate mediators of inflammation by blocking the inflammatory effects of IFNγ, TNFα, or IL-17A. R9-SOCS1-KIR also protected against TNFα or IL-17A mediated damage to the barrier properties of ARPE-19 cells, as evidenced by immunostaining with the tight junction protein, zona occludin 1 (ZO-1), and measurement of transepithelial electrical resistance (TEER). Experimental autoimmune uveitis (EAU) was generated in B10.RIII mice using a peptide of interphotoreceptor retinal binding protein (IRBP161-180) as immunogen. Topical administration of R9-SOCS1-KIR protected ocular structure and function as seen by fundoscopy, optical coherence tomography (OCT), and electroretinography (ERG). The ability R9-SOCS1-KIR to suppress ocular inflammation and preserve barrier properties of retinal pigment epithelium makes it a potential candidate for aqueous treatment of autoimmune uveitis.Highlightspeptide corresponding to the kinase inhibitory region of SOCS-1 linked to poly-arginine (R9-SOCS1-KIR) and its inactive control peptide were chemically synthesized.R9-SOCS1-KIR attenuated pro-inflammatory effects of IFNγ, TNFα, and IL-17 in ARPE-19 cells, thus showing a simultaneous inhibition Th1 and Th17 cell functions.Damage to barrier properties of ARPE-19 cells caused by TNFα or IL-17 was prevented in the presence of R9-SOCS1-KIR.Topical administration of R9-SOCS1-KIR prevented ocular damage in a mouse model of experimental autoimmune uveitis.

Specific humoral immune responses in 12 cases of food sensitization to sesame seed

1997 ◽  
Vol 27 (11) ◽  
pp. 1285-1291 ◽  
Author(s):  
M. N. KOLOPP-SARDA ◽  
D. A. MONERET-VAUTRIN ◽  
B. GOBERT ◽  
G. KANNY ◽  
M. BRODSCHII ◽  
...  
Keyword(s):  
Immune Responses ◽  
Sesame Seed ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Food Sensitization
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