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?