Electromagnetic field-induced stimulation of Bruton's tyrosine kinase

Here we present evidence that exposure of DT40 lymphoma B-cells to low energy electromagnetic fields (EMF) results in activation of phospholipase C-gamma 2 (PLC-gamma 2), leading to increased inositol phospholipid turnover. PLC-gamma 2 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-gamma 2, B-cells rendered BTK-deficient by targeted disruption of the btk gene did not show enhanced PLC-gamma 2 activation in response to EMF exposure. Introduction of the wild-type (but nota 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.