The role of competing mechanisms on Lck regulation

Bozso, Sabin J.; Kang, Jimmy J H; Nagendran, Jeevan

doi:10.1007/s12026-020-09148-2

Cited by 16 publications

(6 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lymphocyte-specific protein tyrosine kinase (LCK), encoded by lck , is a protein tyrosine kinase that binds to CD4 and CD8 molecules and plays a vital role in T cell development and activation ( 52 ). Regulation of LCK activity depends on conformational changes at the plasma membrane induced by phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Exploring the interaction between T-cell antigen receptor-related genes and MAPT or ACHE using integrated bioinformatics analysis

Guo

Gou

et al. 2023

Front. Neurol.

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a neurodegenerative disease that primarily occurs in elderly individuals with cognitive impairment. Although extracellular β-amyloid (Aβ) accumulation and tau protein hyperphosphorylation are considered to be leading causes of AD, the molecular mechanism of AD remains unknown. Therefore, in this study, we aimed to explore potential biomarkers of AD. Next-generation sequencing (NGS) datasets, GSE173955 and GSE203206, were collected from the Gene Expression Omnibus (GEO) database. Analysis of differentially expressed genes (DEGs), gene ontology (GO) functional enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein networks were performed to identify genes that are potentially associated with AD. Analysis of the DEG based protein-protein interaction (PPI) network using Cytoscape indicated that neuroinflammation and T-cell antigen receptor (TCR)-associated genes (LCK, ZAP70, and CD44) were the top three hub genes. Next, we validated these three hub genes in the AD database and utilized two machine learning models from different AD datasets (GSE15222) to observe their general relationship with AD. Analysis using the random forest classifier indicated that accuracy (78%) observed using the top three genes as inputs differed only slightly from that (84%) observed using all genes as inputs. Furthermore, another data set, GSE97760, which was analyzed using our novel eigenvalue decomposition method, indicated that the top three hub genes may be involved in tauopathies associated with AD, rather than Aβ pathology. In addition, protein-protein docking simulation revealed that the top hub genes could form stable binding sites with acetylcholinesterase (ACHE). This suggests a potential interaction between hub genes and ACHE, which plays an essential role in the development of anti-AD drug design. Overall, the findings of this study, which systematically analyzed several AD datasets, illustrated that LCK, ZAP70, and CD44 may be used as AD biomarkers. We also established a robust prediction model for classifying patients with AD.

show abstract

Section: Discussionmentioning

confidence: 99%

Exploring the interaction between T-cell antigen receptor-related genes and MAPT or ACHE using integrated bioinformatics analysis

Guo

Gou

et al. 2023

Front. Neurol.

View full text Add to dashboard Cite

show abstract

“…Together with MYC , LCK, and STAT3 are the nodes of the main network with the highest betweenness centralities ( Supplementary Table S7 ). LCK is a proto-oncogene and an important signalling molecule in the maturation of developing T-cells [ 56 ], contributing to the hematopoietic system and immune system phenotypes in mice [ 53 ], whereas STAT3 is a member of the STAT family of proteins, which mediate cell growth and apoptosis among other processes in response to cytokines and growth factors [ 57 ]. Although there are other proteins with higher betweenness centrality, those were found in small isolated clusters and their betweenness centrality values do not reflect node relevance to the overall network (greyed-out proteins in Supplementary Table S7 ).…”

Section: Resultsmentioning

confidence: 99%

Integration of Stemness Gene Signatures Reveals Core Functional Modules of Stem Cells and Potential Novel Stemness Genes

Barata

Duarte

Futschik

2023

Genes

View full text Add to dashboard Cite

Stem cells encompass a variety of different cell types which converge on the dual capacity to self-renew and differentiate into one or more lineages. These characteristic features are key for the involvement of stem cells in crucial biological processes such as development and ageing. To decipher their underlying genetic substrate, it is important to identify so-called stemness genes that are common to different stem cell types and are consistently identified across different studies. In this meta-analysis, 21 individual stemness signatures for humans and another 21 for mice, obtained from a variety of stem cell types and experimental techniques, were compared. Although we observed biological and experimental variability, a highly significant overlap between gene signatures was identified. This enabled us to define integrated stemness signatures (ISSs) comprised of genes frequently occurring among individual stemness signatures. Such integrated signatures help to exclude false positives that can compromise individual studies and can provide a more robust basis for investigation. To gain further insights into the relevance of ISSs, their genes were functionally annotated and connected within a molecular interaction network. Most importantly, the present analysis points to the potential roles of several less well-studied genes in stemness and thus provides promising candidates for further experimental validation.

show abstract

“…Apart from stabilizing the interaction of the TCR with peptide/HLA class II molecules, CD4 plays a key role in T‐cell activation through activating LCK (reviewed in Refs. [8, 27]). Similar to the interaction of CD4 with HLA class II/peptide complexes, surface binding of anti‐CD4 mAbs (e.g., clone RPA‐T4 and OKT‐4) to CD4 can induce LCK phosphorylation [9].…”

Section: Resultsmentioning

confidence: 99%

Enolase 1 of Candida albicans binds human CD4⁺ T cells and modulates naïve and memory responses

Daud,

Dasari,

Adelfinger

et al. 2023

Eur J Immunol

View full text Add to dashboard Cite

To obtain a better understanding of the biology behind life‐threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti‐CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte‐specific protein tyrosine kinase (LCK), which was also the case for anti‐CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4+ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4+ T‐cell recall responses. Therapeutically, CD4+ T cells transduced with a p41/Crf1‐specific T‐cell receptor developed for adoptive T‐cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4+ T cells with CaEno1 modulated host CD4+ T‐cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4+ T‐cell responses.

show abstract

The role of competing mechanisms on Lck regulation

Cited by 16 publications

References 44 publications

Exploring the interaction between T-cell antigen receptor-related genes and MAPT or ACHE using integrated bioinformatics analysis

Exploring the interaction between T-cell antigen receptor-related genes and MAPT or ACHE using integrated bioinformatics analysis

Integration of Stemness Gene Signatures Reveals Core Functional Modules of Stem Cells and Potential Novel Stemness Genes

Enolase 1 of Candida albicans binds human CD4⁺ T cells and modulates naïve and memory responses

Contact Info

Product

Resources

About

The role of competing mechanisms on Lck regulation

Cited by 16 publications

References 44 publications

Exploring the interaction between T-cell antigen receptor-related genes and MAPT or ACHE using integrated bioinformatics analysis

Exploring the interaction between T-cell antigen receptor-related genes and MAPT or ACHE using integrated bioinformatics analysis

Integration of Stemness Gene Signatures Reveals Core Functional Modules of Stem Cells and Potential Novel Stemness Genes

Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

Contact Info

Product

Resources

About

Enolase 1 of Candida albicans binds human CD4⁺ T cells and modulates naïve and memory responses