CARMA1 is required for Akt-mediated NF-kappaB activation in T cells.
Many details of the generic pathway for induction of NF-kappaB have been delineated, but it is still not clear how multiple, diverse receptor systems are able to converge on this evolutionarily conserved family of transcription factors. Recent studies have shown that the CARMA1, Bcl10, and MALT1 proteins are critical for coupling the common elements of the NF-kappaB pathway to the T-cell receptor (TCR) and CD28. We previously demonstrated a role for the serine/threonine kinase Akt in CD28-mediated NF-kappaB induction. Using a CARMA1-deficient T-cell line, we have now found that the CARMA complex is required for induction of NF-kappaB by Akt, in cooperation with protein kinase C activation. Furthermore, using a novel selective inhibitor of Akt, we confirm that Akt plays a modulatory role in NF-kappaB induction by the TCR and CD28. Finally, we provide evidence for a physical and functional interaction between Akt and CARMA and for Akt-dependent phosphorylation of Bcl10. Therefore, in T cells, Akt impinges upon NF-kappaB signaling through at least two separate mechanisms.
Narayan
Preeti
P
Department of Immunology, BST E-1056, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15261, USA.
Holt
Brittany
B
Tosti
Richard
R
Kane
Lawrence P
LP
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001596:Benzylamines / Q000494:pharmacology; D053468:CARD Signaling Adaptor Proteins; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism; D019169:Jurkat Cells / Q000187:drug effects; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D011810:Quinoxalines / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; C501521:Akt-I-1,2 compound; D051017:Apoptosis Regulatory Proteins; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D001596:Benzylamines; D053468:CARD Signaling Adaptor Proteins; D018106:CD28 Antigens; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011810:Quinoxalines; D011948:Receptors, Antigen, T-Cell; D051058:Oncogene Protein v-akt; D051550:I-kappa B Kinase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C426242:CARD11 protein, human; D006162:Guanylate Cyclase; D013755:Tetradecanoylphorbol Acetate