scholarly journals LCK as a Potential Therapeutic Target for Acute Rejection after Kidney Transplantation: A Bioinformatics Clue

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Linpei Jia ◽  
Rufu Jia ◽  
Yinping Li ◽  
Xiaoxia Li ◽  
Qiang Jia ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
T Cell ◽  
Acute Rejection ◽  
T Cell Receptor ◽  
Protein Interactions ◽  
Therapeutic Target ◽  
Cell Receptor ◽  
Functional Enrichment ◽  
Literature Mining ◽  
Potential Therapeutic Target

Objectives. We aim to identify the key biomarker of acute rejection (AR) after kidney transplantation via bioinformatics methods. Methods. The gene expression data GSE75693 of 30 samples with stable kidney transplantation recipients and 15 AR samples were downloaded and analyzed by the limma package to identify differentially expressed genes (DEGs). Then, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were done to explore the biological functions and potential important pathways of DEGs. Finally, protein-protein interactions (PPIs) and literature mining were applied to construct the cocitation network and to select the hub protein. Results. A total of 437 upregulated genes and 353 downregulated genes were selected according to P<0.01 and log2fold change>1.0. DEGs of AR are mainly located on membranes and impact the activation of receptors in immune responses. In the PPI network, Src kinase, lymphocyte kinase (LCK), CD3G, B2M, interferon-γ, CD3D, tumor necrosis factor, VAV1, and CD3E in the T cell receptor signaling pathway were selected as important factors, and LCK was identified as the hub protein. Conclusion. LCK, via acting on T-cell receptor, might be a potential therapeutic target for AR after kidney transplantation.

scholarly journals Phosphatidylserine binding directly regulates TIM-3 function

2021 ◽  
Vol 478 (17) ◽  
pp. 3331-3349
Author(s):  
Courtney M. Smith ◽  
Alice Li ◽  
Nithya Krishnamurthy ◽  
Mark A. Lemmon
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Therapeutic Target ◽  
Immune Modulation ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
Potential Therapeutic Target ◽  
Signaling Receptors ◽  
Ligand Regulation ◽  
Regulatory Ligands

Co-signaling receptors for the T cell receptor (TCR) are important therapeutic targets, with blockade of co-inhibitory receptors such as PD-1 now central in immuno-oncology. Advancing additional therapeutic immune modulation approaches requires understanding ligand regulation of other co-signaling receptors. One poorly understood potential therapeutic target is TIM-3 (T cell immunoglobulin and mucin domain containing-3). Which of TIM-3's several proposed regulatory ligands is/are relevant for signaling is unclear, and different studies have reported TIM-3 as a co-inhibitory or co-stimulatory receptor in T cells. Here, we show that TIM-3 promotes NF-κB signaling and IL-2 secretion following TCR stimulation in Jurkat cells, and that this activity is regulated by binding to phosphatidylserine (PS). TIM-3 signaling is stimulated by PS exposed constitutively in cultured Jurkat cells, and can be blocked by mutating the PS-binding site or by occluding this site with an antibody. We also find that TIM-3 signaling alters CD28 phosphorylation. Our findings clarify the importance of PS as a functional TIM-3 ligand, and may inform the future exploitation of TIM-3 as a therapeutic target.

scholarly journals Phosphatidylserine binding regulates TIM-3 effects on T cell receptor signaling

2021 ◽  
Author(s):  
Courtney M Smith ◽  
Alice Li ◽  
Nithya Krishnamurthy ◽  
Mark A Lemmon
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Therapeutic Target ◽  
Immune Modulation ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
T Cell Receptor Signaling ◽  
Signaling Receptors ◽  
Ligand Regulation ◽  
Cell Receptor Signaling

Co-signaling receptors for the T cell receptor are important therapeutic targets, with blocking co-inhibitory receptors such as PD-1 now central in immuno-oncology. Advancing additional therapeutic immune modulation approaches requires understanding ligand regulation of other co-signaling receptors. One poorly understood therapeutic target is TIM-3 (T cell immunoglobulin and mucin domain containing-3). Which ligands are relevant for TIM-3 signaling is unclear, and different studies have reported it as co-inhibitory or co-stimulatory. Here, we show that TIM-3 promotes NF-κB signaling and IL-2 secretion following T cell receptor stimulation in Jurkat cells, and is regulated by phosphatidylserine (PS) binding. TIM-3 signaling is stimulated by PS exposed constitutively in cultured Jurkat cells, and can be blocked by mutating the PS-binding site or by occluding this site with an antibody. We also find that TIM-3 signaling alters CD28 phosphorylation. Our findings help clarify conflicting literature results with TIM-3, and inform its exploitation as a therapeutic target.

scholarly journals T cell receptor (TCR) signaling in health and disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kinjal Shah ◽  
Amr Al-Haidari ◽  
Jianmin Sun ◽  
Julhash U. Kazi
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Protein Interactions ◽  
Adaptor Proteins ◽  
Cell Receptor ◽  
Signal Transduction Pathways ◽  
Protein Protein Interactions ◽  
Tcr Signaling

AbstractInteraction of the T cell receptor (TCR) with an MHC-antigenic peptide complex results in changes at the molecular and cellular levels in T cells. The outside environmental cues are translated into various signal transduction pathways within the cell, which mediate the activation of various genes with the help of specific transcription factors. These signaling networks propagate with the help of various effector enzymes, such as kinases, phosphatases, and phospholipases. Integration of these disparate signal transduction pathways is done with the help of adaptor proteins that are non-enzymatic in function and that serve as a scaffold for various protein–protein interactions. This process aids in connecting the proximal to distal signaling pathways, thereby contributing to the full activation of T cells. This review provides a comprehensive snapshot of the various molecules involved in regulating T cell receptor signaling, covering both enzymes and adaptors, and will discuss their role in human disease.

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