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PMID: 15520247 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

The molecular adapter Carma1 controls entry of IkappaB kinase into the central immune synapse.

The Journal of experimental medicine ·Vol. 200 ·No. 9 ·2004-11-01 ·Pages 1167-77

Hara H, Bakal C, Wada T, Bouchard D, Rottapel R, Saito T, Penninger JM

Abstract

Carma1 (also known as caspase recruitment domain [CARD]11, Bimp3) is a CARD-containing membrane-associated guanylate kinase family protein that plays an essential role in antigen receptor-induced nuclear factor kappaB activation. We investigated the role of Carma1 in the assembly of signaling molecules at the immune synapse using a peptide-specific system. We report that Carma1 is essential for peptide-induced interleukin 2 and interferon gamma production, but dispensable for proliferation in T cells. Recruitment and distribution of T cell receptor, lymphocyte function associated 1, lipid rafts, and protein kinase C (PKC)theta; to central and peripheral immune synapse regions occur normally in Carma1-/- T cells. Carma1 controls entry of IkappaB kinase (IKK) into lipid raft aggregates and the central region of the immune synapse, as well as activation of IKK downstream of PKC. Our data provide the first genetic evidence on a new class of molecular scaffold that controls entry of defined signaling components, IKK, into the central supramolecular activation cluster at T cell-antigen-presenting cell interfaces without having any apparent effect on the overall organization and formation of immune synapses.

MeSH Terms
Animals Antigen Presentation/immunology Antigen-Presenting Cells/immunology,metabolism CD4-Positive T-Lymphocytes/immunology Cell Adhesion/immunology Cell Fractionation Flow Cytometry Fluorescent Antibody Technique Guanylate Kinases I-kappa B Kinase Membrane Microdomains/immunology,metabolism Mice Mice, Transgenic Microscopy, Confocal Nucleoside-Phosphate Kinase/immunology,metabolism Protein Kinase C/metabolism Protein Serine-Threonine Kinases/immunology,metabolism Receptors, Antigen, T-Cell/metabolism Signal Transduction/immunology
Chemicals
Receptors, Antigen, T-Cell Protein Serine-Threonine Kinases Chuk protein, mouse I-kappa B Kinase Ikbkb protein, mouse Ikbke protein, mouse Protein Kinase C Nucleoside-Phosphate Kinase Guanylate Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hara Hiromitsu
IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, c/o Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria.
Bakal Christopher
Wada Teiji
Bouchard Denis
Rottapel Robert
Saito Takashi
Penninger Josef M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20032246
Published
2004-11-01
Pages
1167-77
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2211862
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20032246 PMC Full Text View journal details
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