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-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.
Kristupaitis
D
D
Biotherapy Program, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Dibirdik
I
I
Vassilev
A
A
Mahajan
S
S
Kurosaki
T
T
Chu
A
A
Tuel-Ahlgren
L
L
Tuong
D
D
Pond
D
D
Luben
R
R
Uckun
F M
FM
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D002645:Chickens; D004574:Electromagnetic Fields; D004789:Enzyme Activation; D007527:Isoenzymes / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000473:pathology; D051966:Phospholipase C gamma; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D007527:Isoenzymes; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D010738:Type C Phospholipases; D051966:Phospholipase C gamma