| First Author | Patrick MS | Year | 2009 |
| Journal | Proc Natl Acad Sci U S A | Volume | 106 |
| Issue | 38 | Pages | 16345-50 |
| PubMed ID | 19805304 | Mgi Jnum | J:153235 |
| Mgi Id | MGI:4361774 | Doi | 10.1073/pnas.0908593106 |
| Citation | Patrick MS, et al. (2009) Gasp, a Grb2-associating protein, is critical for positive selection of thymocytes. Proc Natl Acad Sci U S A 106(38):16345-50 |
| abstractText | 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. |
