Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation.
Bcl10, a caspase recruitment domain (CARD)-containing protein identified from a breakpoint in mucosa-associated lymphoid tissue (MALT) B lymphomas, is essential for antigen-receptor-mediated nuclear factor kappaB (NF-kappaB) activation in lymphocytes. We have identified a novel CARD-containing 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-kappaB. 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-kappaB.
Gaide
O
O
Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066, Epalinges, Switzerland.
Martinon
F
F
Micheau
O
O
Bonnet
D
D
Thome
M
M
Tschopp
J
J
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004789:Enzyme Activation; D020224:Expressed Sequence Tags; D051528:Guanylate Kinases; D006367:HeLa Cells; D006801:Humans; D008223:Lymphoma / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection; D015854:Up-Regulation
D018076:DNA, Complementary; D016328:NF-kappa B; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases