Electromagnetic Field-induced Stimulation of Bruton's Tyrosine Kinase

Daiva Kristupaitis,Ilker Dibirdik,Alexei Vassilev,Sandeep Mahajan,Tomohiro Kurosaki,Alice Chu,Lisa Tuel-Ahlgren,Dong Tuong,David Pond,Richard Luben,Fatih M Uckun

doi:10.1074/jbc.273.20.12397

Abstract

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-gamma2), leading to increased inositol phospholipid turnover. PLC-gamma2 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-gamma2. B-cells rendered BTK-deficient by targeted disruption of the btk gene did not show enhanced PLC-gamma2 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.

Highlights

We present evidence that exposure of DT40 lymphoma B-cells to low energy electromagnetic fields (EMF) results in activation of phospholipase C-␥ 2 (PLC␥2), leading to increased inositol phospholipid turnover
We previously reported that exposure of B-lineage lymphoid cells to low energy EMF stimulates the protein tyrosine kinase LYN, and activation of LYN kinase was sufficient and mandatory for EMF-induced tyrosine phosphorylation in B-lineage lymphoid cells [10]
To further elucidate the EMF-induced signal transduction events in Blineage lymphoid cells, we decided to examine the enzymatic activity of Bruton’s tyrosine kinase (BTK) in DT40 lymphoma B-cells after EMF exposure using immune complex kinase assays

Summary

Introduction

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

Results

Conclusion