BCL10 mediates lipopolysaccharide/toll-like receptor-4 signaling through interaction with Pellino2.
Toll-like receptor (TLR) pathways signal through microbial components stimulation to induce innate immune responses. Herein, we demonstrate that BCL10, a critical molecule that signals between the T cell receptor and IkappaB kinase complexes, is involved in the innate immune system and is required for appropriate TLR4 pathway and nuclear factor-kappaB (NF-kappaB) activation. In response to lipopolysaccharide (LPS) stimulation, BCL10 was recruited to TLR4 signaling complexes and associated with Pellino2, an essential component down-stream of BCL10 in the TLR4 pathway. In a BCL10-deficient macrophage cell line, LPS-induced NF-kappaB activation was consistently defective, whereas activator protein-1 and Elk-1 signaling was intact. In addition, we found that BCL10 was targeted by SOCS3 for negative regulation in LPS signaling. The recruitment of BCL10 to TLR4 signaling complexes was attenuated by induced expression of SOCS3 in a feedback loop. Furthermore, ectopic SOCS3 expression blocked the interaction between BCL10 and Pellino2 together with BCL10-generated NF-kappaB activation and inducible nitric-oxide synthase expression. Together, these data define an important role of BCL10 in the innate immune system.
Liu
Yingle
Y
Key Laboratory of Virology (Ministry of Education), Department of Biotechnology, College of Life Sciences, Wuhan University, Hubei, Wuhan 430072, People's Republic of China.
Dong
Wei
W
Chen
Lu
L
Xiang
Rong
R
Xiao
Huazhong
H
De
Gejing
G
Wang
Zhimin
Z
Qi
Yipeng
Y
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002460:Cell Line; D008070:Lipopolysaccharides / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C488088:Bcl10 protein, mouse; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C485961:Peli2 protein, mouse; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors