The MAGUK family protein CARD11 is essential for lymphocyte activation.
Members of the MAGUK family proteins cluster receptors and intracellular signaling molecules at the neuronal synapse. We report that genetic inactivation of the MAGUK family protein CARD11/Carma1/Bimp3 results in a complete block in T and B cell immunity. CARD11 is essential for antigen receptor- and PKC-mediated proliferation and cytokine production in T and B cells due to a selective defect in JNK and NFkappaB activation. Moreover, B cell proliferation and JNK activation were impaired upon stimulation of TLR4 with lipopolysaccharide, indicating that CARD11 is involved in both the innate and adaptive immune systems. Our results show that the same family of molecules are critical regulators of neuronal synapses and immune receptor signaling.
Hara
Hiromitsu
H
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 7, A-1030, Vienna, Austria.
Wada
Teiji
T
Bakal
Chris
C
Kozieradzki
Ivona
I
Suzuki
Shinobu
S
Suzuki
Nobutaka
N
Nghiem
Mai
M
Griffiths
Emily K
EK
Krawczyk
Connie
C
Bauer
Birgit
B
D'Acquisto
Fulvio
F
Ghosh
Sankar
S
Yeh
Wen Chen
WC
Baier
Gottfried
G
Rottapel
Robert
R
Penninger
Josef M
JM
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D006162:Guanylate Cyclase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020672:I-kappa B Proteins / Q000276:immunology / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism; D011946:Receptors, Antigen / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D020672:I-kappa B Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011946:Receptors, Antigen; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C426242:CARD11 protein, human; D006162:Guanylate Cyclase