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Silencing of Bruton's tyrosine kinase (Btk) using short interfering RNA duplexes (siRNA)
Author(s) -
Hein Juhana E.,
Smith C.I.Edvard,
Nore Beston F.
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03206-4
Subject(s) - bruton's tyrosine kinase , tyrosine kinase , small interfering rna , microbiology and biotechnology , rna interference , gene silencing , kinase , x linked agammaglobulinemia , transfection , chemistry , biology , rna , signal transduction , biochemistry , gene
Tec family tyrosine kinases, Bruton's tyrosine kinase (Btk), Itk, Bmx, Tec, and Txk, are multi‐domain proteins involved in hematopoietic signaling. Here, we demonstrate that human Btk protein can transiently be depleted using double‐stranded short RNA interference (siRNA) oligonucleotides. Imaging and Western blotting analysis demonstrate that Btk expression is down regulated in heterologous systems as well as in hematopoietic lineages, following transfection or microinjection of Btk siRNA duplexes. The induction of histamine release, a pro‐inflammatory mediator, in RBL‐2H3 mast cells was reduced by 20–25% upon Btk down regulation. Similar, results were obtained when the Btk activity was inhibited using the kinase blocker LFM‐A13. These results demonstrate a direct role of Btk for the efficient secretion of histamine in allergic responses.