Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B.
BCL10 belongs to the caspase recruitment domain (CARD) family of proteins that regulate apoptosis and NF-kappaB signaling pathways. Analysis of BCL10-deficient mice has revealed that BCL10 mediates NF-kappaB activation by antigen receptors in B and T cells. We recently identified a subclass of CARD proteins (CARD9, CARD11, and CARD14) that may function to connect BCL10 to multiple upstream signaling pathways. We report here that CARD10 is a novel BCL10 interactor that belongs to the membrane-associated guanylate kinase family, a class of proteins that function to organize signaling complexes at plasma membranes. When expressed in cells, CARD10 binds to BCL10 and signals the activation of NF-kappaB through its N-terminal effector CARD domain. We propose that CARD10 functions as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-kappaB.
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
L
L
Wang
Y
Y
Guo
W J
WJ
Huang
X
X
Ke
J L
JL
Poyet
G A
GA
Manji
S
S
Merriam
M A
MA
Glucksmann
P S
PS
DiStefano
E S
ES
Alnemri
J
J
Bertin
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001665:Binding Sites; D053468:CARD Signaling Adaptor Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017930:Genes, Reporter; D051528:Guanylate Kinases; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D053468:CARD Signaling Adaptor Proteins; C430880:CARD10 protein, human; C498975:Card10 protein, mouse; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases