CARMA1 mediates T cell receptor (TCR)-induced NF-kappaB activation. However, how TCR links to CARMA1 in the signaling pathway is not clear. Here, we show that CARMA1 is inducibly phosphorylated after TCR-CD28 costimulation. This phosphorylation is likely induced by PKCtheta, since PKCtheta induces phosphorylation of CARMA1 in vitro and in vivo. Our results indicate that the PKCtheta-induced phosphorylation of CARMA1 likely occurs on Ser552 on the Linker region of CARMA1. Importantly, expression of CARMA1 mutant, in which Ser552 is mutated, fails to mediate TCR-induced NF-kappaB activation in CARMA1-deficient T cells. The functional defect of this CARMA1 mutant is likely due to the fact that this mutant cannot be phosphorylated at the critical residue, thereby failing to recruit the downstream signaling components into the immunological synapse. Together, our studies provide the first genetic evidence that the phosphorylation of CARMA1 plays a critical role in the TCR signaling pathway.
Pubmed ID: 16356856 RIS Download
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A collection of both commercial and noncommercial software products which includes: Mascot Distiller, Mascot Parser, and Mascot Server. Mascot Distiller is commercial and provides a single interface to process raw data into de-isotoped peak lists. This tool can also be used for the easy distribution of search and quantitative results to colleagues. The non-commercial Mascot Parser software provides an API (Application Programmer Interface) that makes it easier to access search results written in C++, Java, Python and Perl. Mascot Server is non-commercial, and is a collection of peptide mass fingerprints as well as a MS/MS database. A selection of popular sequence databases are available online and include SwissProt, NCBInr, and the EST divisions of EMBL. This server is best used for evaluating and searching for smaller data sets.
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