title: The MAGUK family protein CARD11 is essential for lymphocyte activation.
abstract: 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.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 7, A-1030, Vienna, Austria.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Hara
authors.forename: Teiji
authors.initials: T
authors.lastname: Wada
authors.forename: Chris
authors.initials: C
authors.lastname: Bakal
authors.forename: Ivona
authors.initials: I
authors.lastname: Kozieradzki
authors.forename: Shinobu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Suzuki
authors.forename: Mai
authors.initials: M
authors.lastname: Nghiem
authors.forename: Emily K
authors.initials: EK
authors.lastname: Griffiths
authors.forename: Connie
authors.initials: C
authors.lastname: Krawczyk
authors.forename: Birgit
authors.initials: B
authors.lastname: Bauer
authors.forename: Fulvio
authors.initials: F
authors.lastname: D'Acquisto
authors.forename: Sankar
authors.initials: S
authors.lastname: Ghosh
authors.forename: Wen Chen
authors.initials: WC
authors.lastname: Yeh
authors.forename: Gottfried
authors.initials: G
authors.lastname: Baier
authors.forename: Robert
authors.initials: R
authors.lastname: Rottapel
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
mesh_terms: 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
chemical_list: 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