Establishing a chemical genetic link between Bruton tyrosine kinase activity in malignant B cells and cell functions involved in the micro-environmental dialogue.

Autor:	Göckeritz, Elisa, Vondey, Verena, Guastafierro, Anna, Pizevska, Maja, Hassenrück, Floyd, Neumann, Lars, Hallek, Michael, Krause, Günter
Předmět:	BIOCHEMICAL genetics PROTEIN-tyrosine kinases B cells CELL physiology CHEMOKINES
Zdroj:	British Journal of Haematology; Sep2017, Vol. 178 Issue 6, p949-953, 5p, 2 Graphs
Abstrakt:	To elucidate their mechanism of action, inhibitors of Bruton tyrosine kinase ( BTK) and resistant BTK mutants were employed to dissect target-dependent cellular functions. BTK-C481S and -T474I, expressed in Ramos and NALM-6 cells, maintained BTK auto-phosphorylation under treatment with ibrutinib or dasatinib, respectively, which showed only modest cytotoxicity. Retained activity of BTK-T474 partially rescued cell migration from inhibition by dasatinib. Importantly, resistant BTK mutants reconstituted B cell receptor-triggered chemokine secretion in the presence of corresponding inhibitors, demonstrating that BTK activity is connected with cell-intrinsic functions of malignant B cells with importance for their dialogue with the micro-environment. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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