Antigen-Receptor Signaling to Nuclear Factor κB

Abstract

Signal transduction events leading to the survival, differentiation, or apoptosis of cells of the innate or adaptive immune system must be properly coordinated to ensure the normal mounting and termination of immune responses. One of the key transcription factors in immune responses is nuclear factor kappaB (NF-kappaB), which has been the focus of intense investigation over the past two decades. With the identification of the CARMA1-BCL10-MALT1 complex and ongoing progress in understanding the molecular mechanisms connecting T cell and B cell receptor proximal signals to the IkappaB kinase (IKK) complex, a cohesive model of antigen receptor (AgR)-dependent signaling to NF-kappaB activation is beginning to emerge. In this review, we provide an overview of the current state of research into the mechanisms that regulate AgR-mediated NF-kappaB transcriptional activity, with particular focus on the events leading to activation of the IKK complex.

Requirement of phospholipase C‐γ2 (PLCγ2) for Dectin‐1‐induced antigen presentation and induction of TH1/TH17 polarization

“…Calcium flux is essential for the activation of NFAT, whereas DAG activates PKC. In T lymphocytes, PKC theta has been shown to promote the formation of a CARMA1/Bcl10/MALT1 complex that activates NF-kB [38]. Thus, PLCg2-generated DAG may activate a PKC isoform in DC, which promotes the formation of the CARD9/ Bcl10/MALT1 complex.…”

Calcium signaling in lymphocytes

“…As a result, several Ca 2+ -dependent signaling proteins and their target transcription factors are activated, including the phosphatase calcineurin and its target NFAT(nuclear factor of activated T cells), CaMK (Ca 2+ -calmodulin-dependent kinase) and its target CREB(cyclic-AMP-responsive-elementbinding protein) MEF2(myocyte enhancer factor 2) which is acted upon by both the calcineurin and CaMK pathways, and NFκB(nuclear factor κB). Simultaneously, DAG production activates the Ras-mitogen activated protein kinase (MAPK) and protein kinase C (PKC) pathways, which in turn lead to activation of the transcription factors AP-1 (a transcriptional complex formed by c-Jun and c-Fos) and NFκB [15,16]. Thus Ca 2+ signaling is integrated with other signaling pathways and the integration occurs at the level of the binding of transcription factors to DNA response elements, resulting in cell proliferation and cytokine gene expression.…”

Cutting Edge: Alternative Signaling of Th17 Cell Development by Sphingosine 1-Phosphate

“…Both inhibitors suppress biochemical pathways coupling G protein-coupled receptors (GPCRs) for some inflammatory mediators to the generation of cytokines, including IL-6 and IL-8, that are critical for inflammatory and metabolic responses (18 -20). In particular, the extension of NF-B involvement to S1P-enhancement of both Th17 cell development and IL-17 generation broadens the spectrum of NF-B contributions to immunological cytokinemediated chronic inflammation (21). The potential involvement of the S1P-S1P 1 axis in several autoimmune diseases had been considered to be attributable solely to the effects on lymphocyte trafficking in lymphoid organs and lymphocyte migration in nonlymphoid target organs (22).…”