Dataset Information

Bcl10 plays a critical role in NF-kappaB activation induced by G protein-coupled receptors.

ABSTRACT: G protein-coupled receptors (GPCRs) play pivotal roles in cell proliferation, differentiation, and survival. Although many studies indicate that the stimulation of GPCRs leads to NF-kappaB activation, the molecular mechanism by which GPCRs induced NF-kappaB activation remains largely unknown. Bcl10 is an essential adaptor molecule connecting antigen receptor signaling cascades to NF-kappaB activation in lymphocytes. However, the function of Bcl10 in nonlymphoid cells remains to be determined. In this study, we demonstrated that the deficiency of Bcl10 resulted in the defect in NF-kappaB activation induced by either expressing the constitutively active mutant of G protein or stimulation of cells with lysophosphatidic acid or endothelin-1, which activate their GPCR. In contrast, TNF-alpha-, LPS-, and integrin-induced NF-kappaB activation was not affected in Bcl10-deficient cells. Together, our results provide genetic evidence showing that Bcl10 is a key signaling component mediating NF-kappaB activation induced by GPCRs in nonlymphoid cells.

SUBMITTER: Wang D

PROVIDER: S-EPMC1765424 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bcl10 plays a critical role in NF-kappaB activation induced by G protein-coupled receptors.

Wang Donghai D You Yun Y Lin Pei-Chun PC Xue Liquan L Morris Stephan W SW Zeng Hu H Wen Renren R Lin Xin X

Proceedings of the National Academy of Sciences of the United States of America 20061219 1

G protein-coupled receptors (GPCRs) play pivotal roles in cell proliferation, differentiation, and survival. Although many studies indicate that the stimulation of GPCRs leads to NF-kappaB activation, the molecular mechanism by which GPCRs induced NF-kappaB activation remains largely unknown. Bcl10 is an essential adaptor molecule connecting antigen receptor signaling cascades to NF-kappaB activation in lymphocytes. However, the function of Bcl10 in nonlymphoid cells remains to be determined. In ...[more]

PMID: 17179215

Similar Datasets

Project description:Platelet-activating factor (PAF), a potent proinflammatory phospholipid mediator, has been implicated in inducing intestinal inflammation in diseases such as inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC). However, its mechanisms of inducing inflammatory responses are not fully understood. Therefore, studies were designed to explore the mechanisms of PAF-induced inflammatory cascade in intestinal epithelial cells.Nuclear factor kappa B (NF-kappaB) activation was measured by luciferase assay and enzyme-linked immunosorbent assay (ELISA), and interleukin 8 (IL-8) production was determined by ELISA. B-cell lymphoma 10 (Bcl10), caspase recruitment domain-containing membrane-associated guanylate kinase protein 3 (CARMA3), and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) mRNA and protein levels were assessed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. siRNA silencing of Bcl10 was used to examine its role in PAF-induced NF-kappaB activation and IL-8 production. The promoter region of the Bcl10 gene was cloned with the PCR method and promoter activity measured by luciferase assay.The adaptor protein Bcl10 appeared to play an important role in the PAF-induced inflammatory pathway in human intestinal epithelial cells. Bcl10 was required for PAF-induced I kappaB alpha phosphorylation, NF-kappaB activation, and IL-8 production in NCM460, a cell line derived from normal human colon, and Caco-2, a transformed human intestinal cell line. PAF also stimulated Bcl10 interactions with CARMA3 and MALT1, and upregulated Bcl10 expression in these cells via transcriptional regulation.These findings highlight a novel PAF-induced inflammatory pathway in intestinal epithelial cells, requiring Bcl10 as a critical mediator and involving CARMA3/Bcl10/MALT1 interactions. The proinflammatory effects of PAF play prominent roles in the pathogenesis of IBD and this pathway may present important targets for intervention in chronic inflammatory diseases of the intestine.

Dataset Information

Bcl10 plays a critical role in NF-kappaB activation induced by G protein-coupled receptors.

Publications

Bcl10 plays a critical role in NF-kappaB activation induced by G protein-coupled receptors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets