CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell activation and found that T cell receptor (TCR) stimulation induced a physical association of CARMA1 with the TCR and Bcl10. We found that CARMA1 was constitutively associated with lipid rafts, whereas cytoplasmic Bcl10 translocated into lipid rafts upon TCR engagement. A CARMA1 mutant, defective for Bcl10 binding, had a dominant-negative (DN) effect on TCR-induced NF-kappa B activation and IL-2 production and on the c-Jun NH(2)-terminal kinase (Jnk) pathway when the TCR was coengaged with CD28. Together, our data show that CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation and CD28 costimulation-dependent Jnk activation.

Bcl10, a caspase recruitment domain (CARD)-containing protein identified from a breakpoint in mucosaassociated lymphoid tissue (MALT) B lymphomas, is essential for antigen-receptor-mediated nuclear factor U UB (NF-U UB) activation in lymphocytes. We have identified a novel CARDcontaining protein and interaction partner of Bcl10, named Carma1. Carma1 is predominantly expressed in lymphocytes and represents a new member of the membrane-associated guanylate kinase family. Carma1 binds Bcl10 via its CARD motif and induces translocation of Bcl10 from the cytoplasm into perinuclear structures. Moreover, expression of Carma1 induces phosphorylation of Bcl10 and activation of the transcription factor NF-U UB. We propose that Carma1 is a crucial component of a novel Bcl10-dependent signaling pathway in T-cells that leads to the activation of NF-U UB. ß

Objective-The goal of this study was to investigate the effects of nonenzymatic glycation on the antiinflammatory properties of apolipoprotein (apo) A-I. Methods and Results-Rabbits were infused with saline, lipid-free apoA-I from normal subjects (apoA-I N ), lipid-free apoA-I nonenzymatically glycated by incubation with methylglyoxal (apoA-I Glyc in vitro ), nonenzymatically glycated lipid-free apoA-I from subjects with diabetes (apoA-I Glyc in vivo ), discoidal reconstituted high-density lipoproteins (