ITK-SYK and TEL-SYK (also known as ETV6-SYK) are human tumor-causing chimeric proteins containing the kinase region of SYK, and the membrane-targeting, N-terminal, PH-TH domain-doublet of ITK or the dimerizing SAM-PNT domain of TEL, respectively. ITK-SYK causes peripheral T cell lymphoma, while TEL-SYK was reported in myelodysplastic syndrome. BTK is a kinase highly related to ITK and to further delineate the role of the N-terminus, we generated the corresponding fusion-kinase BTK-SYK. By generating and analyzing these fusion kinases, we aim to understand the contribution of N-terminal domains to their distinct cellular behavior and oncogenic properties. The fusion kinases were found to behave differently. TEL-SYK showed stronger oncogenic capacity when compared with ITK-SYK and BTK-SYK. Furthermore, ITK-SYK and BTK-SYK triggered IL-3-independent growth of BAF3 pro-B cells. In contrast to BTK-SYK and TEL-SYK, which predominantly localized in perinuclear region and cytoplasm respectively, ITK-SYK exhibits a more diverse cellular distribution, being present in the nucleus, cytoplasm and membrane-bound compartments. Notably, we observed that ITK-SYK undergoes activation-mediated nuclear translocation, a phenomenon that is uncommon among kinases. This unique feature of ITK-SYK is therefore of particular interest due to its potential connection to its transforming capability.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41598-024-83962-8 | DOI Listing |
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700165 | PMC |
Publication Analysis
Top Keywords
Similar Publications
Production of the Key Immunoregulatory Cytokines and the Content of FoxP3 T-Regulatory Lymphocytes in the Epicardial and Thymus Adipose Tissue in Patients with Coronary Heart Disease.
Bull Exp Biol Med
January 2025
Cardiology Research Institute, Tomsk National Research Medical Center, Russian academy of Sciences, Tomsk, Russia.
FoxP3 T-regulatory (Treg) lymphocytes and cytokine production by cells from the stromal vascular fraction (SVF) of epicardial (EAT) and thymus (TAT) adipose tissue of 42 patients with chronic coronary heart disease (CHD) were studied. In the SVF of TAT in patients with Gensini Score (GS)≥74 (the most severe atherosclerosis), the production of IL-1β, TNF, IL-4, and IFNγ was higher, while FoxP3 translocation into the nucleus was lower than in patients with GS<74. The GS index directly correlated with the production of IL-4, IL-1β, and TNF by cells of the SVF of TAT, and inversely - with the production of TNF, IL-17, and IL-10 by cells of the SVF of EAT.
View Article and Find Full Text PDFMitochondrial damage causes inflammation via cGAS-STING signaling in ketamine-induced cystitis.
Inflamm Res
January 2025
Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
Background: Mitochondrial dysfunction and damage can result in the release of mitochondrial DNA (mtDNA) into the cytoplasm, which subsequently activates the cGAS-STING pathway, promoting the onset of inflammatory diseases. Various factors, such as oxidative stress, viral infection, and drug toxicity, have been identified as inducers of mitochondrial damage. This study aims to investigate the role of mtDNA as a critical inflammatory mediator in the pathogenesis of ketamine (KET)-induced cystitis (KC) through the cGAS-STING pathway.
View Article and Find Full Text PDF6-hydroxygenistein attenuates hypoxia-induced injury via activating Nrf2/HO-1 signaling pathway in PC12 cells.
Sci Rep
January 2025
Department of Pharmacy, the First Affiliated Hospital of Xi'an Jiaotong University, NO.277 Yanta West Road, Yanta District, Xi'an, 710061, Shaanxi, People's Republic of China.
4',5,6,7-tetrahydoxyisoflavone (6-hydroxygenistein, 6-OHG) is a hydroxylated derivative of genistein with excellent antioxidant activity, but whether 6-OHG can protect hypoxia-induced damage is unclear. The objective of current study was to evaluate the protective effect and underling mechanism of 6-OHG against hypoxia-induced injury via network pharmacology and cellular experiments. 6-OHG-related and hypoxia injury-related targets were screened by public databases.
View Article and Find Full Text PDFGABAFG isolated fom ginseng ameliorates type 2 diabetes mellitus by modulating gut microbiota and autophagy-lysosome pathway.
J Adv Res
January 2025
College of Chinese Medicinal Materials, Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China. Electronic address:
Introduction: Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic metabolic disease caused by insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of Panax ginseng C.
View Article and Find Full Text PDFPRDX2 promotes gastric cancer progression by forming a feedback loop with PKM2/STAT3 axis.
Cell Signal
January 2025
Department of Clinical Laboratory Medicine, Nantong Tumor Hospital/Affiliated Tumor Hospital of Nantong University, Nantong 226300, China. Electronic address:
Peroxiredoxin 2 (PRDX2) is an antioxidant enzyme that has been reported to be overexpressed in various cancers. However, the role of PRDX2 in gastric cancer progression and its underlying mechanism remains unclear. Herein, we revealed the function of PRDX2 in gastric cancer progression and explored its molecule mechanism.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!