Ku in the cytoplasm associates with CD40 in human B cells and translocates into the nucleus following incubation with IL-4 and anti-CD40 mAb.
CD40 plays a critical role in survival, growth, differentiation, and class switching of B lymphocytes. Although Ku is required for immunoglobulin class switching, how CD40 signal transduction is coupled to Ku is still unknown. Here, we show that CD40 directly interacts with Ku through the membrane-proximal region of cytoplasmic CD40. Ku was confined to the cytoplasm in human primary B cells, and the engagement of CD40 on the B cells cultured in the presence of IL-4 resulted in the dissociation of Ku from CD40, translocation of Ku into the nucleus, and increase in the activity of DNA-dependent protein kinase. These findings indicate that Ku is involved in the CD40 signal transduction pathway and may play an important role in the CD40-mediated events.
Morio
T
T
Department of Pediatrics, Tokyo Medical and Dental University School of Medicine, Japan. tmorio.ped@med.tmd.ac.jp
Hanissian
S H
SH
Bacharier
L B
LB
Teraoka
H
H
Nonoyama
S
S
Seki
M
M
Kondo
J
J
Nakano
H
H
Lee
S K
SK
Geha
R S
RS
Yata
J
J
D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004265:DNA Helicases; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D017578:Immunoglobulin Class Switching; D015847:Interleukin-4 / Q000378:metabolism* / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D000072200:Ku Autoantigen; D008239:Lysine / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015847:Interleukin-4; D014443:Tyrosine; D011392:Proline; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D008239:Lysine