Abstract
BackgroundThe CARMA1-BCL10-MALT1 (CBM) complex bridges T cell receptor (TCR) signaling to the canonical IκB kinase (IKK)/NF-κB pathway. The CBM complex constitutes a signaling cluster of more than 1 Mio Dalton. Little is known about factors that facilitate the rapid assembly and maintenance of this dynamic higher order complex.FindingsHere, we report the novel interaction of the aryl hydrocarbon receptor (AHR) interacting protein (AIP) and the molecular scaffold protein CARMA1. In T cells, transient binding of CARMA1 and AIP enhanced formation of the CBM complex. Thereby, AIP promoted optimal IKK/NF-κB signaling and IL-2 production in response to TCR/CD28 co-stimulation.ConclusionsOur data demonstrate that AIP acts as a positive regulator of NF-κB signaling upon T cell activation.
Highlights
The CARMA1-BCL10-MALT1 (CBM) complex bridges T cell receptor (TCR) signaling to the canonical IκB kinase (IKK)/Nuclear factor-κB (NF-κB) pathway
Assembly of the CARMA1-BCL10-MALT1 (CBM) complex is an essential step in the signal transmission from the T cell receptor (TCR) to the activation of canonical IκB kinase (IKK)/NF-κB signaling [1]
CARMA1 belongs to the family of Membrane-associated guanylate kinase (MAGUK) proteins comprising PDZ, SRC homology 3 (SH3) and Guanylate kinase (GUK) domains in its C-terminus
Summary
The CARMA1-BCL10-MALT1 (CBM) complex bridges T cell receptor (TCR) signaling to the canonical IκB kinase (IKK)/NF-κB pathway. Findings Assembly of the CARMA1-BCL10-MALT1 (CBM) complex is an essential step in the signal transmission from the T cell receptor (TCR) to the activation of canonical IκB kinase (IKK)/NF-κB signaling [1]. Since extensive intramolecular restructuring of the CARMA1 MAGUK region is required to initiate downstream signaling after T cell stimulation [14], we asked if AIP can support conformational changes involved in CBM formation.
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