A requirement for CARMA1 in TCR-induced NF-kappa B activation.
Stimulation of the T cell receptor (TCR) complex initiates multiple signaling cascades that lead to the activation of several transcription factors, including the NF-kappa B family members. Although various proximal signaling components of the TCR have been intensively studied, the distal components that mediate TCR-induced NF-kappa B activation remain largely unknown. Using a somatic mutagenesis approach, we cloned a CARMA1-deficient T cell line. Deficiency in CARMA1 (originally known as CARDII) resulted in selectively impaired activation of NF-kappa B induced by the TCR and a consequent defect in interleukin-2 (IL-2) production. Reconstitution of the CARMA1-deficient cells with CARMA1 fully rescued this signaling defect. Together, our results show that CARMA1 is an essential signaling component that mediates TCR-induced NF-kappa B activation.
Wang
Donghai
D
Department of Microbiology, School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, NY 14214, USA.
You
Yun
Y
Case
Sara M
SM
McAllister-Lucas
Linda M
LM
Wang
Lin
L
DiStefano
Peter S
PS
Nuñez
Gabriel
G
Bertin
John
J
Lin
Xin
X
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins; D006162:Guanylate Cyclase / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000502:physiology*; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D000074121:Protein Kinase C-theta; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*
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; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; C426242:CARD11 protein, human; D006162:Guanylate Cyclase