Regulation of NF-κB pathway in T lymphocytes

The transcription factor NF-KB has a central role in coordinating the expression of a wide variety of genes that control the immune system. Defining the proteins and the mechanisms that transmit signals from the T-cell receptor to NF-KB is therefore an important goal for immunologists. Although most players have probably been identified, relatively little is known about the detailed molecular mechanisms involved in the cascade leading to NF-KB activation following engagement of the T cell receptor by a foreign antigen. PKC theta, CARMA1, BCL-10, MALT1 and caspase 8 are signalling proteins that have a key role in antigen receptor-mediated lymphocyte activation through the NF-KB pathway. In this review, we discuss recent insights into this specific signal transduction cascade, and the way it is regulated. Several lines of evidence, mainly from biochemical studies of T cells clearly indicate that phosphorylation, ubiquitination and degradation are key control elements in the positive and negative regulation of the NF-KB pathway in response to TCR stimulation.