The intracellular signal cascades involved in chemokine-stimulated migration of in vitro activated human peripheral blood CD4+ T-lymphocytes were investigated. IP-10-mediated chemotactic response of lymphocytes was decreased in the presence of selective inhibitors of Src-kinases (by 40-45%), PI3-kinases (35-40%), and MAP-kinases ERK1/2 (35-40%) and p38 (20%). Combined addition of specific inhibitors of Src-kinases and PI3-kinases and inhibitors of Src-kinases and ERK1/2 MAP-kinases did not result in the further increase of the inhibitory effect, while the combined addition of specific inhibitors of PI3-kinases and ERK1/2 MAP-kinases decreased migration of CD4+ T-lymphocytes more effectively (by 55-60%) than any individual inhibitor. Immunoblotting analysis of activation of MAP-kinases ERK1/2 and p38 revealed increased level of phosphorylation of ERK1/2 and p38 MAP-kinases in the presence IP-10. Selective inhibitors of Src-kinases and PI3-kinases significantly inhibited phosphorylation of p38 but did not influence phosphorylation of ERK1/2 MAP-kinases. Our results suggest that Src-kinases, PI3-kinases, and ERK1/2 MAP-kinases are involved in intracellular signal cascade activated during IP-10-stimulated migration of T-lymphocytes, whereas p38 MAP-kinases do not participate in the migration process, although its activation induced by IP-10 depends on Src-kinases and PI3-kinases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s10541-005-0165-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dasatinib-Induced Gynecomastia: A Case Report.
Cureus
December 2024
Medical Oncology, Jawaharlal Nehru Medical College, Wardha, IND.
Gynecomastia, the abnormal enlargement of male breast tissue, is a rare side effect associated with dasatinib. This drug is used in the treatment of chronic myeloid leukemia (CML). We present a case of dasatinib-induced gynecomastia in a 52-year-old gentleman with CML who developed bilateral breast enlargement and tenderness after approximately four months of dasatinib treatment.
View Article and Find Full Text PDFMolecular Pharmacology of Dasatinib Provides Unique Insights into the Mechanistic Basis of Success and Failure of Targeted Cancer Therapy.
ACS Pharmacol Transl Sci
January 2025
Department of Cell and Molecular Biology, University of Rhode Island, 120 Flagg Rd, Kingston, Rhode Island 02881, United States.
Despite the enthusiasm for targeted cancer therapies in preclinical studies and the success of a select few drugs, many promising drug candidates fail in clinical trials. The gap between preclinical promise and clinical outcomes underscores the need to investigate factors influencing the success or failure of targeted therapies. Dasatinib, an inhibitor of Abl and Src protein tyrosine kinases, is highly effective toward chronic myeloid leukemia (CML) by targeting BCR-Abl, but it is ineffective against solid tumors when targeting Src kinases.
View Article and Find Full Text PDFIntegrating machine learning and structure-based approaches for repurposing potent tyrosine protein kinase Src inhibitors to treat inflammatory disorders.
Sci Rep
January 2025
State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.
Tyrosine-protein kinase Src plays a key role in cell proliferation and growth under favorable conditions, but its overexpression and genetic mutations can lead to the progression of various inflammatory diseases. Due to the specificity and selectivity problems of previously discovered inhibitors like dasatinib and bosutinib, we employed an integrated machine learning and structure-based drug repurposing strategy to find novel, targeted, and non-toxic Src kinase inhibitors. Different machine learning models including random forest (RF), k-nearest neighbors (K-NN), decision tree, and support vector machine (SVM), were trained using already available bioactivity data of Src kinase targeting compounds.
View Article and Find Full Text PDFSRC enhanced cisplatin resistance in bladder cancer by reprogramming glycolysis and pentose phosphate pathway.
Commun Biol
January 2025
Institute of Urology, The Second Hospital of Lanzhou University, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, Gansu, China.
The development of cisplatin resistance often results in a grim prognosis in advanced or recurrent bladder cancer. However, effective treatment strategies for cisplatin resistance have not been well established. Herein, we found that overactivation of SRC is associated with cisplatin-resistance.
View Article and Find Full Text PDFPrevention of radiotherapy-induced pro-tumorigenic microenvironment by SFK inhibitors.
Theranostics
January 2025
College of Pharmacy, Research Institute of Pharmaceutical Sciences and Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea.
Radiotherapy is a widely employed technique for eradication of tumor using high-energy beams, and has been applied to approximately 50% of all solid tumor patients. However, its non-specific, cell-killing property leads to inevitable damage to surrounding normal tissues. Recent findings suggest that radiotherapy-induced tissue damage contributes to the formation of a pro-tumorigenic microenvironment.
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!