A critical role of TAK1 in B-cell receptor-mediated nuclear factor kappaB activation.
The kinase TAK1 is essential for T-cell receptor (TCR)-mediated nuclear factor kappaB (NF-kappaB) activation and T-cell development. However, the role of TAK1 in B-cell receptor (BCR)-mediated NF-kappaB activation and B-cell development is not clear. Here we show that B-cell-specific deletion of TAK1 impaired the transition from transitional type 2 to mature follicular (FO) B cells and caused a marked decrease of marginal zone (MZ) B cells. TAK1-deficient B cells exhibited an increase of BCR-induced apoptosis and impaired proliferation in response to BCR ligation. Importantly, TAK1-deficient B cells failed to activate NF-kappaB after BCR stimulation. Thus, TAK1 is critical for B-cell maturation and BCR-induced NF-kappaB activation.
Schuman
James
J
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee 53226, USA.
Chen
Yuhong
Y
Podd
Andrew
A
Yu
Mei
M
Liu
Hong-Hsing
HH
Wen
Renren
R
Chen
Zhijian J
ZJ
Wang
Demin
D
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000378:metabolism*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020930:MAP Kinase Kinase Kinases / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D000099151:MAP Kinase Kinase Kinase 7
D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D000099151:MAP Kinase Kinase Kinase 7