Faculty Opinions recommendation of The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.

Author(s):  
Neil Barclay
2011 ◽  
Vol 7 (12) ◽  
pp. e1002432 ◽  
Author(s):  
Ildar Gabaev ◽  
Lars Steinbrück ◽  
Claudia Pokoyski ◽  
Andreas Pich ◽  
Richard J. Stanton ◽  
...  

2021 ◽  
Author(s):  
Jiali Zhang ◽  
Erwei Zuo ◽  
Minfang Song ◽  
Li Chen ◽  
Zhenzhou Jiang ◽  
...  

THEMIS plays an indispensable role in T cells, but its mechanism of action is highly controversial. Using the systematic proximity labeling methodology PEPSI, we identified THEMIS as an uncharacterized substrate for the phosphatase SHP1. Saturated mutagenesis analysis revealed that THEMIS phosphorylation at the evolutionally conserved Tyr34 residue was oppositely regulated by SHP1 and the kinase LCK. Like THEMIS-/- mice, THEMIS Y34F/Y34F knock-in mice showed a significant decrease in CD4 thymocytes and mature CD4 T cells, but a normal thymic development and peripheral homeostasis of CD8 T cells. Mechanistically, phosphorylated THEMIS induced by TCR activation acts as a "priming substrate" to bind SHP1 and convert its phosphatase activity from basal level to nearly fully activated level, ensuring an appropriate negative regulation of TCR signaling. However, cytokine signaling in CD8 T cells failed to elicit THEMIS Y34 phosphorylation, revealing both phosphorylation-dependent and -independent roles of THEMIS in controlling T cell maturation and expansion.


2020 ◽  
Vol 31 (7-8) ◽  
pp. 423-439 ◽  
Author(s):  
Henning Olbrich ◽  
Sebastian J. Theobald ◽  
Constanze Slabik ◽  
Laura Gerasch ◽  
Andreas Schneider ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Chengquan Shen ◽  
Jing Liu ◽  
Jirong Wang ◽  
Xiaokun Yang ◽  
Haitao Niu ◽  
...  

PTPN6 (protein tyrosine phosphatase nonreceptor type 6), a tyrosine phosphatase, is known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Previous studies have demonstrated that PTPN6 expression is relatively elevated in several malignancies. However, the role of PTPN6 in bladder cancer (BC) remains unclear. The purpose of this study was to explore the prognostic value of PTPN6 in BC. RNA-seq data from The Cancer Genome Atlas (TCGA) was used to identify the expression level of PTPN6 in BC. The relationship between clinical pathologic features and PTPN6 were analyzed with the Wilcoxon signed-rank test. The prognostic and predictive value of PTPN6 was evaluated by survival analysis and nomogram. Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential molecular mechanisms of PTPN6 in BC. Finally, Tumor Immune Estimation Resource (TIMER) was applied to investigate the relationship between PTPN6 and immune cell infiltration in the tumor microenvironment. Results indicated that PTPN6 was overexpressed in BC tissues compared with normal bladder tissues and was significantly correlated with grade, stage, T, and N. Survival analysis showed that low expression of PTPN6 was significantly related to the poor overall survival (OS) in BC patients. Coexpression analysis showed that PTPN6 and TNFRSF14 (Tumor necrosis factor receptor superfamily member 14) have a close correlation in BC. GSEA showed that multiple cancer-associated signaling pathways are differentially enriched in the PTPN6 high expression phenotype. Moreover, the expression level of PTPN6 was positively associated with the infiltration of B cells, CD4+T cells, dendritic cells, and neutrophils and negatively associated with CD8+ T cells and macrophages in BC. In conclusion, we identified that PTPN6 may be a novel prognostic biomarker in BC based on the TCGA database. Further clinical trials are needed to confirm our observations and mechanisms underlying the prognostic value of PTPN6 in BC also deserve further experimental exploration.


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