BTK as a mediator of radiation-induced apoptosis in DT-40 lymphoma B cells.
Bruton's tyrosine kinase (BTK) is a member of the SRC-related TEC family of protein tyrosine kinases (PTKs). DT-40 lymphoma B cells, rendered BTK-deficient through targeted disruption of the btk gene by homologous recombination knockout, did not undergo radiation-induced apoptosis, but cells with disrupted lyn or syk genes did. Introduction of the wild-type, or a SRC homology 2 domain or a plecstrin homology domain mutant (but not a kinase domain mutant), human btk gene into BTK-deficient cells restored the apoptotic response to radiation. Thus, BTK is the PTK responsible for triggering radiation-induced apoptosis of lymphoma B cells, and its kinase domain is indispensable for the apoptotic response.
Uckun
F M
FM
Molecular Signal Transduction Laboratory, Biotherapy Institute, University of Minnesota, Roseville, MN 55113, USA.
Waddick
K G
KG
Mahajan
S
S
Jun
X
X
Takata
M
M
Bolen
J
J
Kurosaki
T
T
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000528:radiation effects*; D002645:Chickens; D005720:Gamma Rays; D018390:Gene Targeting; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000502:physiology; D014407:Tumor Cells, Cultured; D018909:src Homology Domains
D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human