Electromagnetic Field-induced Stimulation of Bruton's Tyrosine Kinase

• Published in: The Journal of biological chemistry 1998-05, Vol.273 (20), p.12397-12401
• Main Authors: Kristupaitis, Daiva, Dibirdik, Ilker, Vassilev, Alexei, Mahajan, Sandeep, Kurosaki, Tomohiro, Chu, Alice, Tuel-Ahlgren, Lisa, Tuong, Dong, Pond, David, Luben, Richard, Uckun, Fatih M.
• Format: Article
• Language: English
• Subjects: Agammaglobulinaemia Tyrosine Kinase; Animals; Chickens; Electromagnetic Fields; Enzyme Activation; Isoenzymes - metabolism; Lymphoma, B-Cell - enzymology; Lymphoma, B-Cell - pathology; Phospholipase C gamma; Protein-Tyrosine Kinases - metabolism; Tumor Cells, Cultured; Type C Phospholipases - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.20.12397

Here we present evidence that exposure of DT40 lymphoma B-cells to low energy electromagnetic fields (EMF) results in activation of phospholipase C-γ 2 (PLC-γ2), leading to increased inositol phospholipid turnover. PLC-γ2 activation in EMF-stimulated cells is mediated by stimulation of the Bruton's tyrosine kinase (BTK), a member of the Src-related TEC family of protein tyrosine kinases, which acts downstream of LYN kinase and upstream of PLC-γ2. B-cells rendered BTK-deficient by targeted disruption of thebtk gene did not show enhanced PLC-γ2 activation in response to EMF exposure. Introduction of the wild-type (but not a kinase domain mutant) human btk gene into BTK-deficient B-cells restored their EMF responsiveness. Thus, BTK exerts a pivotal and mandatory function in initiation of EMF-induced signaling cascades in B-cells.