Characterisation of the functions of SLy1 and SLy2 in the immune system

• Antragstellerin: Professorin Dr. Sandra Beer-Hammer
• Fachliche Zuordnung: Immunologie
• Förderung: Förderung von 2006 bis 2014
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 31333905

SLy (SH3-lymphocyte protein) 1 and SLy2 are novel paralogous genes coding for putative adaptor proteins in lymphocytes. Characteristic features of SLy proteins are an N-terminal bipartite nuclear localisation signal (NLS), a src homology 3 domain (SH3) and a C-terminal sterile alpha motif (SAM). Antigen receptor stimulation causes rapid phosphorylation of SLy1 at Serine 27 in a PI3K- and PKC-dependent manner. In a first approach, we generated a mouse line expressing a mutant version of SLy1 with a deletion encompassing the NLS signal and Ser27 by gene targeting (SLy1d). Sly1d/d mice revealed profound immunological defects in T and B cell functions (Beer et al, 2005, MCB). As predicted, the mutant SLy1 protein, in contrast to the wildtype version, failed to shuttle between the cytoplasmic and the nuclear cellular compartments. As for SLy2 no functional data are available. Hence, the scientific aim of this proposal is the elucidation of the molecular functions of the SLy1 and SLy2 proteins in immunity. This will be achieved by the generation of SLy1- and SLy2-single gene deficient as well as SLy1/2-double deficient mouse lines followed by phenotype analysis. To this end, we have already established murine embryonic stem cell lines with targeted inactivations of the SLy1 and SLy2 genes.

• DFG-Verfahren: Sachbeihilfen