Regulation of Bcl10 by serine 231 (87.2)

Abstract

Abstract Bcl10 is a component of the “CBM” complex of proteins, along with CARMA and MALT1. This complex regulates activation of the NF-κB-inducing IKK kinase complex, and is important for integrating signals from antigen receptors and co-receptors on T and B lymphocytes. We previously showed that activation of NF-κB by the Akt kinase in T cells requires an intact CBM complex, and that Akt may interact with - and regulate the phosphorylation of - one or more members of the complex. Using the online ScanSite algorithm, we identified serine 231 in Bcl10 as a possible site of Akt phosphorylation. We generated a form of Bcl10 in which serine 231 has been mutated to alanine (S231A), and assessed effects on Bcl10 function. Thus, the S231A form of Bcl10 activates the NF-κB pathway much less efficiently in T cells, compared with the wild-type protein. Paradoxically, NF-κB activation by S231A Bcl10 is enhanced in fibroblasts. In both cell types, expression levels of S231A Bcl10 are consistently lower than the wild-type protein. Finally, we have examined the role of S231 in the regulation of Bcl10 localization. However, in contrast to its effects on NF-κB activation, mutation of S231 appears to have no impact on sub-cellular localization of Bcl10. These results suggest that phosphorylation of Bcl10 at S231 is important for regulation of NF-κB and that this pathway may operate differently in T cells and fibroblasts. Supported by the Ovarian Cancer Research Fund.