Gasp, a Grb2-associating protein, is critical for positive selection of thymocytes.
T cells develop in the thymus through positive and negative selection, which are responsible for shaping the T cell receptor (TCR) repertoire. To elucidate the molecular mechanisms involved in selection remains an area of intense interest. Here, we identified and characterized a gene product Gasp (Grb2-associating protein, also called Themis) that is critically required for positive selection. Gasp is a cytosolic protein with no known functional motifs that is expressed only in T cells, especially immature CD4/CD8 double positive (DP) thymocytes. In the absence of Gasp, differentiation of both CD4 and CD8 single positive cells in the thymus was severely inhibited, whereas all other TCR-induced events such as beta-selection, negative selection, peripheral activation, and homeostatic proliferation were unaffected. We found that Gasp constitutively associates with Grb2 via its N-terminal Src homology 3 domain, suggesting that Gasp acts as a thymocyte-specific adaptor for Grb2 or regulates Ras signaling in DP thymocytes. Collectively, we have described a gene called Gasp that is critical for positive selection.
Pubmed ID: 19805304 RIS Download
Animals | Blotting, Western | CD4-Positive T-Lymphocytes | CD8-Positive T-Lymphocytes | Cell Line | Cytosol | Flow Cytometry | Gene Expression | Humans | Immunophenotyping | Immunoprecipitation | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | Proteins | Receptors, Antigen, T-Cell | Reverse Transcriptase Polymerase Chain Reaction | Spleen | T-Lymphocytes | Thymus Gland