Determining the destiny of NF-kappa B after TCR ligation: it's CARMA1.
In T lymphocytes, the "novel" protein kinase C theta (PKC theta) isoform and the transcription factor nuclear factor-kappaB (NF-kappaB) are required for cell proliferation and the production of cytokines in response to T cell activation; however, the molecular interactions that link PKCtheta and NF-kappaB have remained unknown. Two recent reports demonstrate that CARMA1 (caspase recruitment domain-containing membrane-associated guanylate kinase protein-1) bridges the gap between PKCtheta and the IkappaB kinase (IKK)-dependent activation of NF-kappaB in T cells. Excessive T lymphocyte activation and proliferation are hallmarks of T cell-derived leukemias. Given that CARMA1 is specifically expressed in lymphoid tissues, could pharmacological inhibitors be designed to inhibit CARMA1's (or PKCtheta's) ability to promote the activation of NF-kappaB?
Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. sbunnell@helix.nih.gov
Stephen C
SC
Bunnell
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D018442:Lymphoma, B-Cell, Marginal Zone / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D000074121:Protein Kinase C-theta; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*
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; D002352:Carrier 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; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; C426242:CARD11 protein, human; D006162:Guanylate Cyclase