Disease relevance of CARD11

• The expression levels of CARMA1 and BCL10 were examined immunohistochemically in 30 patients with lymphoma [1].
• RESULTS: CARMA1 mRNA was detected in 55% of lymphoma patients but in only 17% of chronic gastritis patients [1].
• In addition, CARMA1 expression was positive more frequently in patients of DLBL without MALT lymphoma (100%) than in patients of MALT lymphoma (51%) [1].
• The expression of CARMA1 and CARD9 was frequent in the Helicobacter pylori-negative patients (100% and 86%, respectively), in the API2-MALT1 chimeric transcript-positive patients (100% and 100%, respectively), and in the specimens from patients who did not respond to H. pylori eradication (76% and 71%, respectively) [1].

High impact information on CARD11

• Phosphorylation of CARMA1: the link(er) to NF-kappaB activation [2].
• CARMA1 mediates T cell receptor (TCR)-induced NF-kappaB activation [3].
• Furthermore, PKCbeta interacted with the serine-rich CARMA1 linker, and both PKCbeta and PKCtheta phosphorylated identical serine residues (S564, S649, and S657) within this linker [4].
• Our results indicate that the PKCtheta-induced phosphorylation of CARMA1 likely occurs on Ser552 on the Linker region of CARMA1 [3].
• Along with reports that the CARMA1 MAGUK scaffold protein coordinates activation of Jnk and NF-kappaB but not of p38 or NFAT, our findings identify MAGUK scaffold proteins as 'orchestrators' of TCR signal specificity [5].

Biological context of CARD11

• Screening of a mouse thymus cDNA library yielded CARD11, a membrane-associated guanylate kinase (MAGUK) family member containing CARD, PDZ, SH3 and GUK domains [6].
• Moreover, expression of Carma1 induces phosphorylation of Bcl10 and activation of the transcription factor NF-kappaB [7].
• Using a somatic mutagenesis approach, we cloned a CARMA1-deficient T cell line [8].
• The CARMA1 signalosome links the signalling machinery of adaptive and innate immunity in lymphocytes [9].

Anatomical context of CARD11

• We report here that CARD protein 11 (CARD11) and CARD protein 14 (CARD14) are novel CARD-containing proteins that belong to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane [10].
• CARMA1 plays a critical role in mediating activation of the NFkappaB transcription factor following antigen receptor stimulation of both B and T lymphocytes [11].
• Carma1 is predominantly expressed in lymphocytes and represents a new member of the membrane-associated guanylate kinase family [7].
• CONCLUSIONS: The overexpression of CARMA1 and CARD9 presumably is associated with the development or progression of gastric B-cell lymphoma, especially among patients who have disease in which the pathogenesis is not related to H. pylori [1].
• Given that CARMA1 is specifically expressed in lymphoid tissues, could pharmacological inhibitors be designed to inhibit CARMA1's (or PKCtheta's) ability to promote the activation of NF-kappaB [12]?

Physical interactions of CARD11

• CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD) [13].
• We also demonstrated that the cytoplasmic tail of CD26 interacts with CARMA1 in T-cells, resulting in signaling events that lead to NF-kappaB activation [14].

Regulatory relationships of CARD11

• 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 [13].
• A requirement for CARMA1 in TCR-induced NF-kappa B activation [8].

Other interactions of CARD11

• These findings suggest that CARD11 and CARD14 are novel MAGUK family members that function as upstream activators of BCL10 and NF-kappaB signaling [10].
• Physical and functional interaction of CARMA1 and CARMA3 with Ikappa kinase gamma-NFkappaB essential modulator [11].
• CARMA proteins are scaffold molecules that contain a caspase recruitment domain and a membrane-associated guanylate kinase-like domain [11].
• CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation [13].
• Together, these results indicate that CARMA1 mediates CD3/CD28 costimulation-induced NF-kappaB activation by recruiting downstream signaling components into the immunological synapse [15].

Analytical, diagnostic and therapeutic context of CARD11

• Determining the destiny of NF-kappa B after TCR ligation: it's CARMA1 [12].
• RESULTS: To realize the full benefits of performing analysis of variance on microarray data we have developed CARMA, a microarray analysis platform that reads data files generated by most microarray image processing software packages, performs ANOVA using a user-defined linear model, and produces easily interpretable graphical and numeric results [16].

References